High-dose Intravenous Immunoglobulin Therapy Research Articles

Peripheral Nerve and Muscle Disorders Associated with Sjögren's Syndrome

Sjögren's syndrome is often accompanied by various neurological complications, among which peripheral neuropathy is the most common. A variety of clinical phenotypes of peripheral neuropathy, including axonal polyneuropathy and sensory ataxic neuropathy are reported in the literature. We present an overview of the pathophysiology and differential diagnosis of each phenotype. Immunotherapy using corticosteroids and high-dose intravenous immunoglobulin therapy tends to elicit varied therapeutic responses depending on the peripheral neuropathy phenotype. We also discuss myositis, a possible complication of Sjögren's syndrome.

Altered antibody titers in patients with neuromuscular diseases after high-dose intravenous immunoglobulin therapy

We investigated the changes in antibody titers after intravenous immunoglobulin (IVIg) administration in patients with neuromuscular diseases. Among patients who received IVIg from April 1, 2020, to August 31, 2022, we retrospectively evaluated 15 patients with antibody measurements before and after IVIg administration for any rise in the following antibody levels and examined the data for subsequent changes of false positive results to negative ones. The levels of anti SS-A, anti-thyroglobulin, anti-thyroid peroxidase, anti-glutamic acid decarboxylase, HBs, and HBc antibodies transiently increased after IVIg administration and showed false-positive results. However, levels of rheumatoid factor and anti-nuclear and antineutrophil cytoplasmic antibodies were not elevated. The false-positive results became negative after 3 months. Here, we report on the changes in antibody levels before and after IVIg administration and note that levels of hepatitis B virus-related antibodies and various autoantibodies transiently rise after IVIg administration.

Protocolized polyoma BK viral load monitoring and high-dose immunoglobulin treatment in children after kidney transplant.

BKPyV virus nephropathy (BKPyVAN) is diagnosed in 5%-16% of pediatric renal transplant recipients (PRTR) and preceded by BKPyV-viruria and DNAemia. Despite the risk of irreversible transplant damage associated with BKPyVAN, evidence-based consensus guidelines for BKPyVAN prevention are still lacking. In this retrospective study, we examined the safety and efficacy of high-dose intravenous immunoglobulin (HD-IVIG) therapy for prevention of BKPyVAN in PRTR with significant BKPyV-viruria/DNAemia. Between January 2013 and December 2022, all PRTR under our care underwent routine urine and blood testing for BKPyV viral load, using specific polymerase chain reaction (PCR). BKPyV DNAemia, with<103 copies/mL, with BKPyV viruria<107 copies/mL, with no evidence of BKPyVAN, were managed with 50% dose reduction of mycophenolate mofetil (MMF). Patients showing no decline in BKPyV viral load within two months of MMF dose reduction were managed with HD-IVIG (2g/kg). Seventy patients were recruited during a ten-year period and 31/70 patients (44%) demonstrated significant post-transplantation BKPyV-viruria/DNAemia, while 13/31 (42%) patients were unresponsive to MMF dose reduction, and were administered HD-IVIG. Of these, 12/13 (92%) patients achieved BKPyV viral clearance within six months from completion of HD-IVIG therapy and 1/13 patient (8%) was unresponsive to HD-IVIG therapy, showing increased BKPyV viral load. There were no major adverse events associated with HD-IVIG, and none of our patients developed BKPyVAN during the study period. Prophylactic HD-IVIG therapy in PRTR with significant BKPyV-viruria/DNAemia unresponsive to MMF dose reduction is safe and might be effective in preventing BKPyVAN. Our findings remain to be established by large-scale prospective studies.

Successful Adjunctive Treatment of Bilateral Diffuse Uveal Melanocytic Proliferation (BDUMP) with High-Dose Intravenous Immunoglobulin Therapy (IVIG).

Successful Adjunctive Treatment of Bilateral Diffuse Uveal Melanocytic Proliferation (BDUMP) with High-Dose Intravenous Immunoglobulin Therapy (IVIG).

Intravenous Immunoglobulin for Autoimmune Bullous Diseases: A Case Series from a Central European Referral Center.

Background and Objectives: Autoimmune bullous diseases (AIBDs) may be treated with intravenous immunoglobulin (IVIG) infusions. This study aimed to evaluate the benefits and safety profiles of high-dose IVIG therapy in AIBD patients, as determined by clinical remission, the glucocorticosteroid-sparing effect, and adverse events at 12 months follow-up in a Central European university dermatology department setting. Materials and Methods: Our case series included 10 patients: five patients with pemphigus vulgaris, one with pemphigus herpetiformis, one with pemphigus foliaceus, one with bullous pemphigoid, two with epidermolysis bullosa acquisita. They underwent 4-12 monthly cycles of IVIG therapy at a dose of 2 g/kg per cycle. Results: The prednisone dosage reduction after 2, 6, and 12 months following the final IVIG course was 65.45%, 70.91%, and 76.37%, respectively. During the 12-month observation period, disease relapse was observed in 20% of patients, while others achieved complete or partial remission without or with minimal therapy. Side effects were seen in 80% of patients; they were transient and did not necessitate discontinuation of IVIG. Conclusions: IVIG demonstrates effectiveness as a treatment with a favorable safety profile. Nevertheless, its high cost remains a significant drawback, particularly in low-income countries. IVIG should be considered, especially in patients opposed to standard therapies or with contraindications to their use.

Comparison of high-dose IVIG and rituximab versus rituximab as a preemptive therapy for de novo donor-specific antibodies in kidney transplant patients

De novo donor-specific antibody (dnDSA) is associated with a higher risk of kidney graft failure. However, it is unknown whether preemptive treatment of subclinical dnDSA is beneficial. Here, we assessed the efficacy of high-dose intravenous immunoglobulin (IVIG) and rituximab combination therapy for subclinical dnDSA. An open-label randomized controlled clinical trial was conducted at two Korean institutions. Adult (aged ≥ 19 years) kidney transplant patients with subclinical class II dnDSA (mean fluorescence intensity ≥ 1000) were enrolled. Eligible participants were randomly assigned to receive rituximab or rituximab with IVIG at a 1:1 ratio. The primary endpoint was the change in dnDSA titer at 3 and 12 months after treatment. A total of 46 patients (24 for rituximab and 22 for rituximab with IVIG) were included in the analysis. The mean baseline estimated glomerular filtration rate was 66.7 ± 16.3 mL/min/1.73 m2. The titer decline of immune-dominant dnDSA at 12 months in both the preemptive groups was significant. However, there was no difference between the two groups at 12 months. Either kidney allograft function or proteinuria did not differ between the two groups. No antibody-mediated rejection occurred in either group. Preemptive treatment with high-dose IVIG combined with rituximab did not show a better dnDSA reduction compared with rituximab alone.Trial registration: IVIG/Rituximab versus Rituximab in Kidney Transplant With de Novo Donor-specific Antibodies (ClinicalTrials.gov Identifier: NCT04033276, first trial registration (26/07/2019).

Refractory Pediatric NMDA Receptor Encephalitis: A Case Series

Objective To characterize clinical features of our institution's refractory pediatric NMDA receptor encephalitis (NMDARE) patients, in the hopes of identifying predictive risk factors and specific treatment escalation targets. Background Management protocols for pediatric NMDARE increasingly recommend anti-CD-20 agents following first-line treatment with high-dose corticosteroids, intravenous immunoglobulin (IVIg), and/or plasma exchange therapy (PLEX). Even with early, aggressive treatment, some patients exhibit refractory disease or recurrences. Identification of clinical predictors for refractory disease course may allow earlier, targeted treatment escalation in these patients. Design/Methods We performed IRB-approved retrospective, descriptive review of patients in our institutional NMDARE database (2011-2021). Refractory disease was defined as lack of neurological improvement within 1-3 months, or recurrent relapse, after standardized treatment protocol (steroids, IVIg or PLEX, and two doses of rituximab 500 mg/m2). Demographics, clinical information, and diagnostic results from refractory patients were collected. Results 8/73 (10.9%) patients met criteria for refractory NMDARE (median age 10.0 years, IQR 8.3-14.0. 2 male, 6 female). Median days from symptom onset to first treatment was 12.5 (IQR 8.5-18.8), to detection of +NMDA Ab was 20.5 (17.8-24.0), and to rituximab was 27.5 (26.5-31.0). All were critically ill at disease onset, with seizures, encephalopathy, and respiratory failure. 2 (25%) had associated ovarian teratoma. Oligoclonal bands were tested in 6, with 4 resulting positive (67%). 7 had confirmed B-cell depletion after rituximab. Post-rituximab NMDA titers persisted in serum in 5 (63%) and CSF in 8 (100%). Immune therapy escalation was varied, and included repeat rituximab, mycophenolate, cyclophosphamide, and tocilizumab. Conclusions Severe initial presentation is a consistent feature among our refractory patients. The contribution of other factors such as oligoclonal bands and time to diagnosis/treatment are less clear, and warrant inter-group comparison with non-refractory patients. Persistence of serum and CSF titers despite B-cell depletion may suggest utility in targeting CD-20-negative mature plasma cells which may continue to produce disease-causing antibodies.

A comprehensive narrative review of the cutaneous manifestations associated with COVID-19.

The systemic and respiratory clinical manifestations of coronavirus disease 2019 (COVID-19) include fever, coughing, sneezing, sore throat, rhinitis, dyspnea, chest pain, malaise, fatigue, anorexia and headache. Moreover, cutaneous manifestations have been reported in 0.2% to 20.4% of cases. Early diagnosis of COVID-19 leads to a better prognosis; knowledge of its cutaneous manifestations is one way that may help fulfil this goal. In this review, PubMed and Medline were searched with the terms "dermatology", "skin" and "cutaneous", each in combination with "SARS-CoV-2" or "COVID-19". All articles, including original articles, case reports, case series and review articles published from the emergence of the disease to the time of submission, were included. In this comprehensive narrative review, we tried to provide an analysis of the cutaneous manifestations associated with COVID-19, including maculopapular rash, urticaria, Chilblain-like, vesicular lesions, livedo reticularis and petechiae in asymptomatic/symptomatic COVID-19 patients that might be the first complication of infection after respiratory symptoms. Immune dysregulation, cytokine storms, side effects of antiviral drugs, environmental conditions and high-dose intravenous immunoglobulin (IVIG) therapy might be involved in the pathogenesis of the cutaneous manifestations in COVID-19 patients. Therefore, knowledge of cutaneous COVID-19 manifestations might be vital in achieving a quick diagnosis in some COVID-19 patients, which would help control the pandemic. Further research is very much warranted to clarify this issue.

The EIF2AK4/rs4594236 AG/GG Genotype Is a Hazard Factor of Immunoglobulin Therapy Resistance in Southern Chinese Kawasaki Disease Patients.

Background: Kawasaki disease (KD) is an acute, self-limited vasculitis disorder of unknown etiology in children. Immunologic abnormalities were detected during the acute phase of KD, which reflected that the effect cells of the activated immune system markedly increased cytokine production. High-dose intravenous immunoglobulin (IVIG) therapy is effective in resolving inflammation from KD and reducing occurrence of coronary artery abnormalities. However, 10%–20% of KD patients have no response to IVIG therapy, who were defined as IVIG resistance. Furthermore, these patients have persistent inflammation and increased risk of developing coronary artery aneurysm (CAA). EIF2AK4 is a stress sensor gene and can be activated by pathogen infection. In addition, the polymorphisms of EIF2AK4 were associated with various blood vessel disorders. However, it remains unclear whether the EIF2AK4 gene polymorphisms were related to IVIG therapy outcome in KD patients. Methods: EIF2AK4/rs4594236 polymorphism was genotyped in 795 IVIG response KD patients and 234 IVIG resistant KD patients through TaqMan, a real-time polymerase chain reaction. The odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to assess the strength of association between EIF2AK4/rs4594236 polymorphism and IVIG therapeutic effects. Results: Our results showed that the EIF2AK4/rs4594236 AG/GG genotype was significantly associated with increased risk to IVIG resistance compared to the AA genotype (AG vs. AA: adjusted ORs = 1.71, 95% CIs = 1.17–2.51, and p = 0.0061; GG vs. AA: adjusted ORs = 2.09, 95% CIs = 1.36–3.23, and p = 0.0009; AG/GG vs. AA: adjusted ORs = 1.82, 95% CIs = 1.27–2.63, and p = 0.0013; and GG vs. AA/AG: adjusted ORs = 1.45, 95% CI = 1.04–2.02, and p = 0.0306). Furthermore, the stratified analysis of age and gender in the KD cohort indicated that male patients carrying the rs4594236 AG/GG genotype tends to be more resistant to IVIG therapy than female patients. Conclusion: These results suggested that EIF2AK4/rs4594236 polymorphism might be associated with increased risk of IVIG resistance in southern Chinese KD patients.

A case of a 14 year old male with MOGAD (Myelin Oligocyte Glycoprotein Antibody Disease) post-COVID-19 infection responsive to high dose corticosteroids and intravenous immunoglobulin (IVIG) therapy (P9-1.001)

A case of a 14 year old male with MOGAD (Myelin Oligocyte Glycoprotein Antibody Disease) post-COVID-19 infection responsive to high dose corticosteroids and intravenous immunoglobulin (IVIG) therapy (P9-1.001)

P047 The triple M threat of check-point inhibitors - an emerging overlap syndrome

Abstract Background/Aims The objective of this abstract is to raise awareness on an emerging overlap syndrome of life-threatening immune-related adverse events, manifesting as a triad of myositis, myocarditis and myasthenia gravis in immune check-point inhibitor (ICI) treated patients. It highlights the success of combination, aggressive and prompt immunosuppression with high dose intravenous steroid, cyclophosphamide, rituximab and intravenous immunoglobulin therapy, in two patients presenting at Guy’s and St Thomas’s Hospital, London with this overlap syndrome following pembrolizumab therapy. Methods Case presentation. Case 1: 75-year-old Caucasian gentleman receives one dose of pembrolizumab for metastatic melanoma. Two weeks later, he presents with myalgia, weakness, elevated CK 10,000. Troponin T is raised 459, ECG shows right bundle branch block (RBBB) and on day 3, he rapidly descends into complete heart block then cardiac arrest. Return of spontaneous circulation is obtained and a permanent pacemaker (PPM) inserted. On day 6, myocardial biopsy confirms acute myocarditis. He develops progressive muscle weakness, dysphagia and Type 2 respiratory failure. He receives 3 doses of IV methylprednisolone, in addition to intravenous immunoglobulins (IVIG) and intravenous cyclophosphamide. EMG shows mild myopathic features, positive AChR antibody, SSA/Ro60 and myositis-specific SRP antibodies and he becomes dependent on non-invasive ventilation. He commences pyridostigmine for myasthenia gravis. On day 19 two doses 1g Rituximab two weeks apart is administered. Monthly IVIG continues for three months and he completes 6 cycles of 500mg cyclophosphamide. A year following discharge, he is maintained on prednisolone 5mg OD with no additional immunosuppression and significantly improved muscle strength. Case 2: 77-year-old Caucasian gentleman receives one dose of pembrolizumab for metastatic melanoma. Four weeks later, he presents with myalgia, bilateral ptosis, muscle weakness and breathlessness. Bloods show CK 6467, troponin T 1058. He promptly receives 3 doses of IV methylprednisolone in addition to IVIG. A PPM is inserted electively as ECGs show RBBB and intermittent bradyarrhythmias. His anti-Ro/SSA-52 antibody is positive and AChR and myositis-specific antibodies are negative. He trials neostigmine due to persistent ptosis. On Day 6, muscle biopsy confirms immune-mediated necrotising myositis and he commences intravenous cyclophosphamide 500mg followed by 5 further cycles. On day 7, 1g intravenous rituximab is administered and repeated two weeks later, additional to monthly IVIG for five months. 6 months later, his CK has normalised and he has no residual muscle weakness. Results n/a Conclusion Although a rare complication of ICIs, this triad of myositis, myocarditis and myasthenia gravis can be potentially severe and fatal. With ICI reshaping the prognosis of several cancers and pembrolizumab gaining recent further approvals, we will increasingly encounter this therapeutic challenge. Therefore, raising awareness of this overlap syndrome amongst rheumatologists is even more critical to allow for prompt recognition and treatment with immunosuppression. Disclosure A. Mootoo: None. A. Masood: None. P. Maghsoudlou: None. D. D'Cruz: None.

Pharmacologic interventions for Kawasaki disease in children: A network meta-analysis of 56 randomized controlled trials

SummaryBackgroundAlthough the current consensus recommends a standard treatment of high-dose intravenous immunoglobulin with high-dose aspirin to manage Kawasaki disease (KD), the use of different adjunctive therapies remains controversial. The aim of the current network meta-analysis (NMA) was to compare the efficacy and tolerability of different existing interventions for the initial and refractory stages of KD.MethodsAn NMA of randomised controlled trials (RCTs) was conducted using the frequentist model applied after electronic searches in PubMed, Embase, ScienceDirect, ProQuest, ClinicalTrials.gov, ClinicalKey, Cochrane CENTRAL, and Web of Science. The main outcomes were reduced fever duration/diminished severity of fever subsided. The initial stage of KD was defined as the first stage to treat patients with KD; the refractory stage of KD represents KD patients who failed to respond to standard KD treatment. The cut-off points for intravenous immunoglobulin (IVIG) were low (100–400 mg), medium (1 g), and high (at least 2 g).FindingsA total of fifty-six RCTs with 6486 participants were included. NMA demonstrated that the medium-dosage IVIG + aspirin + infliximab [mean difference=−1.76 days (95% confidence intervals (95% CIs): −3.65 to 0.13 days) compared to high-dosage IVIG + aspirin] exhibited the shortest fever duration; likewise, the medium-dosage IVIG + aspirin + infliximab [odds ratio (OR)=0.50, 95% CIs: 0.18–1.37 compared to high-dosage IVIG + aspirin] exhibited the smallest incidence of coronary artery lesion (CAL) in the initial-stage KD. In the refractory-stage KD, the high-dosage IVIG + pulse steroid therapy (OR=0.04, 95% CIs: 0.00–0.43 compared to the high-dosage IVIG only) had the best rate of decline of fever; likewise, the high-dosage IVIG + ciclosporin [OR=0.05 (95% CIs: 0.00–1.21) compared to the high-dosage IVIG only] exhibited the smallest incidence of CAL. Infliximab significantly improved resolution compared to the high-dosage IVIG only group (OR=0.20, 95%CIs: 0.07–0.62) in refractory-stage KD.InterpretationThe NMA demonstrated that the combination therapy with the standard therapy of IVIG and aspirin might have an additional effect on shortening the duration of fever and lowering the CAL incidence rate in patients with acute KD. Moreover, the combination therapy with high-dose IVIG and pulse steroid therapy or cyclosporine therapy might have an additional effect on improving the rate of decline of fever and lowering the incidence rate of CAL in children with refractory KD. Because some of the findings of this NMA should be considered hypothesis-generating rather than confirmatory, further evidence from de novo randomised trials is needed to support our results.FundingNone.

Эффективность высокодозовой внутривенной иммуноглобулинотерапии у детей с расстройствами аутистического спектра, ассоциированными с генетическим дефицитом ферментов фолатного цикла

Обоснование. Ранее неоднократно сообщали об эффективности внутривенной иммуноглобулинотерапии у некоторых детей с расстройствами спектра аутизма без уточнения критерия отбора потенциальных ответчиков на иммунотерапию. Цель исследования: оценить эффективность и безопасность высокодозовой иммуноглобулинотерапии при расстройствах аутистического спектра у детей с генетическим дефицитом фолатного цикла. Материалы и методы. Исследуемую группу составили 78 детей в возрасте от 2 до 10 лет, которые принимали в/в иммуноглобулин в дозе 2 г/кг/мес на протяжении 6 месяцев. В контрольную группу вошли дети аналогичного возрастного и гендерного распределения, которые получали лишь немедикаментозную реабилитационную поддержку. Выявляли замены нуклеотидов MTHFR677 С &gt; Т, MTHFR1298 А &gt; С, MTRR A/G и MTR A/G в различных комбинациях методом полимеразной цепной реакции. Динамику психических симптомов оценивали при помощи шкалы Aberrant Behavior Checklist. Результаты и обсуждение. Достигнуто полное устранение фенотипа расстройств аутистического спектра у 21 пациента и выраженная положительная динамика еще у 33 детей исследуемой группы (p &lt; 0,05; Z &lt; Z0,05). Параллельно отмечалась положительная динамика со стороны других клинических проявлений фенотипа дефицита фолатного цикла: PANDAS (у 19 из 21), эпилептического (у 29 из 36) и кишечного (у 49 из 68 детей) синдромов (p &lt; 0,05; Z &lt; Z0,05). Не отмечено положительной динамики со стороны симптомов поражения пирамидных путей (p &gt; 0,05; Z &gt; Z0,05). Отмечено снижение суммарной вирусной нагрузки и повышение количества естественных киллеров в крови (p &lt; 0,05; Z &lt; Z0,05). Почти полное устранение симптомов лейкоэнцефалопатии в исследуемой группе отмечалось у 29 пациентов, а выраженная положительная динамика — еще в 24 случаях (p &lt; 0,05; Z &lt; Z0,05). Выводы. Внутривенный иммуноглобулин оказывает комплексное положительное воздействие на проявления генетического дефицита фолатного цикла, включая расстройства спектра аутизма, экстрапирамидные нарушения, кишечный синдром, эпилептиформную активность мозга, иммунодефицит и лейкоэнцефалопатию.

Impact of Early Treatment With High-Dose Intravenous Immunoglobulin on Incidence of Kawasaki Disease Complications in Iranian Children.

Objective: Kawasaki disease (KD) occurs in five-year-old or younger children. This study aimed to evaluate the impact of high-dose intravenous immunoglobulin plus acetylsalicylic acid therapy on the prevention and treatment of coronary artery lesions and to evaluate the impact of high-dose acetylsalicylic acid (ASA) on the hearing of the patients. Materials and methods: In this retrospective cohort study, 31 patients with KD were followed from January 2012 to December 2015. The clinical, para-clinical, color Doppler echocardiogram and audiometry results were evaluated. Results: Overall, seven cases (22.6%) developed coronary artery aneurysm (CAA) in the acute phase of the disease, of whom only two still had CAA at the end of the treatment (6%). One of the five children with CAA recovery had a delay in the onset of treatment and one of two patients with persistent CAA at the end of treatment was admitted within the first 10 days. There was no evidence-based abnormal liver biochemical test. None of the patients developed sensorineural hearing loss (SNHL) on audiometry tests conducted before and after treatment. Conclusion: Recovery of coronary artery lesions was 71.43% after 28 days of the onset of treatment. The distribution of coronary artery aneurysm was not different in terms of the time of the treatment initiation (P-Value = 0.371). None of the children had a sensorineural hearing loss (SNHL) 48 hours and 4 weeks after treatment.

Abstract 10512: Sialic Acid-rich Fc Having A Strong Anti-inflammatory Effect In Kawasaki Disease Model

Introduction: Kawasaki disease (KD), which is the most common multisystem vasculitis with unknown causes in childhood, causes coronary artery (CA) aneurysms. High-dose intravenous immunoglobulin (IVIG) is the most standard treatment. However, the problem with current high-dose IVIG therapy is that it is inefficient for both patients and cost because it contains ineffective parts and requires a high total dose. It has recently been reported that sialic acid in the fragment crystallizable (Fc) region has an anti-inflammatory effect. Hypothesis: In the KD model, a small amount of sialic acid-rich (SR-)Fc has an anti-inflammatory effect equivalent to that of high-dose IVIG. Methods: A Candida albicans cell wall extract (CAWE)-induced KD-like vasculitis model was established in DBA/2 mice. IgG, antigen-binding fragment (Fab), and Fc with 2g/kg/0.5ml, and IgG, SR-IgG, and SR-Fc with 0.2g/kg/0.5ml, and placebo 0.5ml were administered intraperitoneally 3 times every other day (n=5, respectively). Four weeks after treatment, we compared the incidence of CA inflammation between each group. Histological analysis was performed by using a quantified scoring system: grade 1; &amp;lt;20 cells /HPF, grade 2; &amp;lt;100cells/HPF, grade 3; &amp;gt;100cels/HPF, grade 4; distraction of elastic lamina, grade 5; neointimal proliferation. Results: All five mice in placebo group had the infiltration grade 3 or higher (100%), whereas none of the mice in IgG group had the infiltration (0%). In Fab group, three out of four had the infiltration (75%, one mouse died), whereas in Fc group, only one out of five had the infiltration (20%). In one-tenth dose IgG group, two out of four had the infiltration (50%, one mouse died), whereas in one-tenth dose SR-IgG and SR-Fc group, 20% or less of them had the infiltration (one out of five, zero out of five, respectively). Treatment with one-tenth dose SR-IgG and SR-Fc significantly suppressed CAWE-induced vasculitis ( p &amp;lt;0.05 and 0.01, respectively). Conclusions: It was shown that the immunoglobulin effect was mainly in the Fc region and one-tenth dose SR-Fc had an anti-inflammatory effect equivalent to that of high-dose IgG in a Candida -induced KD mouse model. One-tenth doses SR-Fc may be an alternative treatment to high-dose IVIG in KD patients.

Use of Intravenous Immunoglobulin in the Treatment of Severe COVID-19 Disease – A Case Series

Objective: To study and document the outcomes of adjuvant use of high dose intravenous immunoglobulin (IVIg) therapy in patients with severe or critical corona virus disease 2019 (COVID-19). We report in a case series of five patients who were admitted with severe and critical COVID-19 disease and were treated with adjuvant IVIG along-with the institute's standard of care (SOC) treatment. Methods: It is a retrospective observational study. We retrospectively collected data on all patients with COVID-19 disease who were hospitalized in author’s unit. The severe and critical disease patients who received IVIg were shortlisted and are discussed. Results: Data from 101 patients were analyzed. Of them 5 patients were treated with IVIG along with institution’s SOC. 4 patients were male and 1 was female. Except one patient (P2) all were above 60 years of age and all had one or more co morbidities with Diabetes mellitus (DM) and Hypertension (HT) present all of them. 3 patients had past history of pulmonary tuberculosis (P1, P4 and P5). P2 had chronic kidney disease (CKD) and P4 had coronary artery disease (CAD) with cardiac resynchronization therapy (CRT) device in situ. Median length of stay was 13 days and 4 of them were discharged. Conclusions: This small case series demonstrates that administration of IVIg in patients with severe COVID-19 disease, who did not respond to usual standard of care treatment, could improve clinical outcome and reduce mortality rate. It should be especially considered in cases with severe critical COVID-19 disease along with evidence of hyper inflammation /cytokine storm. Clinical efficacy is possibly driven by its anti-cytokine effects, reduction of inflammation by inhibition of complement activation, and down-regulation of B and T cells’ functions. Among the various inflammatory markers IVIg reduced CRP and D Dimer levels. It did not show relevant effect on other inflammation markers. However, multicenter studies with large sample size are needed to substantiate these observations.

High Dose Intravenous Immunoglobulin Therapy for Autoimmune Diseases of the Central Nervous System

High-dose intravenous immunoglobulin (IVIg) therapy has pharmacological suppressive actions against phagocytosis, complement system, pathogenic autoantibodies, and inflammatory cytokines, making it an effective treatment for autoimmune diseases. Unfortunately, there is no established evidence of the efficacy of IVIg therapy for autoimmune diseases of the central nervous system. Patients who are resistant to steroids and other immunosuppressive therapies or have complications that preclude the use of strong immunosuppressive therapies are considered eligible for IVIg therapy. The advantages of IVIg therapy include safety and ease of use. However, further evidence of the efficacy of IVIg treatment for autoimmune diseases of the central nervous system is warranted.

大剂量静脉注射免疫球蛋白在重症皮肤病治疗中的应用进展

大剂量静脉注射免疫球蛋白在重症皮肤病治疗中的应用进展

Kawasaki disease with acute myocarditis in an adolescent.

A previously healthy 16-year-old adolescent was admitted to our hospital with fever, sore throat, diarrhoea, strawberry tongue, rashes on lower extremities, and pain in the neck, abdomen and joints. He was initially diagnosed with IgA vasculitis triggered by acute pharyngitis. Despite antibiotic treatment, he gradually developed multiorgan failure and cardiac shock. Cardiac catheterisation did not show any signs of coronary artery disease. Subsequently, he developed serious rhabdomyolysis and peripheral extremity necrosis, suggesting peripheral arteritis. Although blood culture results were negative, he received endotoxin adsorption therapy, but it was ineffective. Hence, we suspected Kawasaki disease (KD). We administered high-dose intravenous immunoglobulin therapy (2 g/kg), which was effective. He gradually recovered without major complications and was given ambulatory discharge 43 days after admission. Early diagnosis and administration of intensive care in adolescents with KD with acute myocarditis are critical but challenging.

The Benefits and Respective Side-Effects of PE Therapy for Intractable Kawasaki Disease.

Kawasaki disease (KD) is a vasculitis syndrome that frequently develops coronary artery lesions (CALs). In the treatment of KD, the utility of high-dose intravenous immuno-globulin (IVIG) therapy has already been clarified, and it has been established as the first-line treatment method. However, since approximately 10% of patients are refractory to this IVIG therapy and 2.6% of all patients have coronary sequelae, 500 children with KD still remain every year in Japan. In this disease, it is necessary to calm inflammation within 10 days of onset in order to suppress CALs caused by a large amount of persistent inflammatory cytokines. Indeed, the early suppression of inflammation is an effective means of suppressing the onset of CALs. Here, we describe the pathophysiology of Kawasaki disease and plasma exchange (PE), which is a therapeutic method that can calm the hyper-cytokine state of this disease. The treatment result of PE for IVIG-refractory Kawasaki disease is outstanding, and an extremely large effect can be expected if it can be started before the appearance of CALs. It seems that it should always be considered as one of the powerful additional treatments in the future.