Including Intravenous Immunoglobulin Research Articles

Efficacy and safety of eculizumab in Guillain-Barré syndrome: A phase 3, multicenter, double-blind, randomized, placebo-controlled clinical trial.

Guillain-Barré syndrome (GBS) is an acute, self-limited, immune-mediated peripheral neuropathy. Current treatments for GBS include intravenous immunoglobulin (IVIg) and plasma exchange, which may not sufficiently benefit severely affected patients. This study evaluated the efficacy and safety of eculizumab add-on therapy to IVIg (standard-of-care treatment) in patients with severe GBS. This phase 3, multicenter, double-blind, randomized, placebo-controlled clinical trial (NCT04752566), enrolled Japanese adults (age ≥ 18 years) with severe GBS (Hughes functional grade [FG] score FG3 or FG4/FG5 within 2 weeks of onset of GBS). Participants were randomized 2:1 to receive intravenous infusion of eculizumab or placebo (once weekly for 4 weeks) with IVIg treatment with 20 weeks of follow-up. Primary efficacy endpoint was the time to first reach FG score ≤1 (able to run). Key secondary endpoints were proportion of participants achieving FG ≤1 at weeks 8 and 24 and FG improvement ≥3 at week 24. Pharmacodynamic analysis of serum free C5 concentration over time was performed. Safety was evaluated. The analysis included 57 participants (eculizumab, n = 37; placebo, n = 20). Primary endpoint was not achieved (hazard ratio, 0.9; 95% CI, 0.45-1.97; p = .89). Key secondary endpoints did not reach statistical significance. Serum C5 concentration was reduced by 99.99% at 1 h postdose and sustained to week 5 but returned to baseline at the end of follow-up period. No new safety signals for eculizumab were identified. Although well tolerated, eculizumab treatment did not show significant effects on motor function recovery compared to placebo in patients with GBS.

Outcomes of rituximab as treatment for immune thrombocytopenic purpura in patients who have failed steroids or IVIG: A retrospective study in a community practice.

e23256 Background: Immune thrombocytopenic purpura (ITP) is a challenging disorder with multiple treatment options. The 2019 American Society of Hematology guidelines outline treatment recommendations for ITP which include intravenous immunoglobulin (IVIG) and steroids as first-line, with Thrombopoietin receptor agonists (TPO-RAs) and Rituximab as second-line agents. They favor TPO-RAs over Rituximab but suggest that the choice should be individualized. In this study, we explore the rate and duration of response to Rituximab as a second-line agent for ITP. We also analyze relapse rates and response to sequential TPO-RAs. Methods: A retrospective study of patients with ITP managed in a community practice from 2018 to 2022. The practice’s electronic medical records were searched for the keywords “ITP” and “Rituximab”. 87 patients fit the search terms. We included patients above age 18 treated with Rituximab for ITP after failing steroids or IVIG. We excluded duplicates, incomplete medical records, patients given Rituximab for reasons other than ITP, patients treated with medications other than steroids or IVIG prior to Rituximab, and patients given less than 4 doses of Rituximab. 60 out of 87 patients were eligible. The primary outcome was response to Rituximab defined as platelets above 30,000 per microliter of blood after 12 weeks of its initiation. Secondary outcomes include relapse rate, duration of response, and subsequent response to TPO-RAs. Secondary outcomes were determined by chart-reviewing physician documentation. Results: SAS 9.4 (SAS/STAT Inst., Carry NC) was used for all data. Categorical variables were quoted as absolute numbers and relative frequencies. A test result was considered statistically significant if p < 0.05. For categorical variables, likelihood ratio chi-square, and Fisher’s exact tests were conducted for 2*2 and r*c contingency tables to test associations. 96.7% of eligible patients responded to Rituximab (P < 0.0001), however 46.7% relapsed. 42.9% of relapses happened in less than 1 year, 14.3% in 1 year, 21.4% in 2 years, 7.1% in 3 years, 10.7% in 4 years, and 3.6% in 5 or more years (P = 0.0043). The response rate to TPO-RAs after Rituximab failure was 88%. No significant toxicity from Rituximab was noted beyond previously reported minor side effects, and there was no treatment-related death. Conclusions: The response rate to Rituximab was 96.7% (P < 0.0001) which was sustained in 53.3% of patients. Most relapsed patients responded well to TPO-RAs. These numbers are very comparable to previously reported response to Rituximab. Therefore, we believe that the strategy of using Rituximab as second-line and reserving TPO-RAs for non-responders is clinically-effective and certainly cost-effective given the fact that Rituximab is administered over four weeks as compared to the often lifetime treatment with TPO-RAs.

Late cognitive and adaptive outcomes of patients with neuroblastoma-associated opsoclonus-myoclonus-ataxia-syndrome: A report from the Children's Oncology Group.

Opsoclonus-myoclonus-ataxia syndrome (OMAS) is a rare autoimmune disorder of the nervous system presenting with abnormal eye and limb movements, altered gait, and increased irritability. Two to four percent of children diagnosed with neuroblastoma have neuroblastoma-associated OMAS (NA-OMAS). These children typically present with non-high-risk neuroblastoma that is cured with surgery, with or without chemotherapy. Despite excellent overall survival, patients with NA-OMAS can have significant persistent neurological and developmental issues. This study aimed to describe long-term neurocognitive and adaptive functioning of patients with NA-OMAS treated with multimodal therapy, including intravenous immunoglobulin (IVIG) on Children's Oncology Group (COG) protocol ANBL00P3. Of 53 children enrolled on ANBL00P3, 25 submitted evaluable neurocognitive data at diagnosis and at least one additional time point within 2years and were included in the analyses. Adaptive development was assessed via the Vineland Adaptive Behavior Scale, and validated, age-appropriate measures of intellectual function were also administered. Twenty-one of the 25 patients in this cohort ultimately received IVIG. Descriptive spaghetti plots suggest that this cohort demonstrated stable long-term cognitive functioning and adaptive development over time. This cohort also demonstrated decreased OMAS scores over time consistent with improved OMAS symptoms. While statistical significance is limited by small sample size and loss to follow-up over 10years, findings suggest stable long-term cognitive and adaptive functioning over time in this treated cohort.

Binocular Diplopia in Miller Fisher Syndrome Pediatric Patient: A Rare Case Report

Introduction : Miller Fisher Syndrome (MFS) is a rare variant of Guillain-Barré syndrome that usually presents with ataxia, areflexia and ophthalmoplegia. It is more common among patients in their 40s and number of cases in pediatric patients is significantly smaller. Our objective is to report a rare case of diplopia in Miller Fisher.
 Case Illustration : An 11 years old boy came with complaint of double vision and history of gaze restriction. Patient had history of inpatient admission due to acute progressive generalized limb weakness and walking difficulty followed by respiratory failure. Patient also had history of chewing and swallowing difficulty. Inpatient treatment included intravenous immunoglobulin (IVIG) for 5 days which resultedin clinical improvement. Electromyography examination done while hospitalization showed normal results. Orthoptic examination revealed 15 degrees exotropia of left eye with 30 prism dioptres (PD) at near and far distance. Worth four dot test resulted in cross diplopia with no abnormality in head CT scan. After 2 months follow-up with push-up pencil exercise, patient showed improvement of symptoms.
 Discussion : MFS is a clinical diagnosis that can be assessed by clinical triad of ataxia, areflexia and ophthalmoplegia. Diagnosis can be supported by ancillary test such as cerebrospinal fluid analysis, electrophysiologic studies or antibody anti-GQ1b . Treatment of MFS are mainly for supportive care with respiratory support and immunotherapy if needed in severe cases.
 Conclusion : The outcome of MFS is usually good with a complete recovery. The improvements generally begin within two to four weeks after the onset of neurological symptoms and complete within six months.

Modern aspects of diagnosis and treatment of chronic inflammatory demyelinating polyneuropathy in children

Analysis of demographic, clinical, laboratory, electrophysiological and neuroimaging data and pathogenetic therapy of pediatric patients with chronic inflammatory demyelinating polyneuropathy (CIDP). Patients (n=30) were observed in a separate structural unit of the Russian Children's Clinical Hospital of the Russian National Research Medical University named after. N.I. Pirogova Ministry of Health of the Russian Federation in the period from 2006 to 2023. The examination was carried out in accordance with the recommendations of the Joint Task Force of the European Federation of Neurological Societies and the Peripheral Nerve Society on the Management of CIDP (2021). All patients received immunotherapy, including intravenous immunoglobulin (IVIG) (n=1), IVIG and glucocorticosteroids (GCS) (n=17, 56.7%), IVIG+GCS+plasmapheresis (n=12, 40.0%). Alternative therapy included cyclophosphamide (n=1), cyclophosphamide followed by mycophenolate mofetil (n=1), rituximab (n=2, 6.6%), azathioprine (n=3), mycophenolate mofetil (n=2, 6.6%). In all patients, there was a significant difference between scores on the MRCss and INCAT functional scales before and after treatment. At the moment, 11/30 (36.6%) patients are in clinical remission and are not receiving pathogenetic therapy. The median duration of remission is 48 months (30-84). The longest remission (84 months) was observed in a patient with the onset of CIDP at the age of 1 year 7 months. Early diagnosis of CIDP is important, since the disease is potentially curable; early administration of pathogenetic therapy provides a long-term favorable prognosis.

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Kawasaki disease (KD) is a self-limited febrile illness diagnosed based on various clinical manifestations, including fever. The major complication of KD is systemic vasculitis, particularly involving the coronary artery. The etiology of KD is not clear, but the pathogenesis may be related to excessive activation of the immune system. Immune modulation for KD treatment, including intravenous immunoglobulin (IVIG), is based on the control of immune hyperactivation. Many studies have reported a genetic susceptibility to KD, which is related to immune cell activation (ITPKC, CAPS3, BLK, FCGR2A, etc.). The innate immunity of humans begins to recognize and react through pattern recognition receptors against pathogen-associated molecular patterns (PAMPs) or damage-associated molecular patterns (DAMPs). Among receptors, the nucleotide-binding domain and leucine-rich repeat-containing receptor (NLRP) or NOD-like receptor (NLRs) in the cytosol contribute to inflammation as a key component. Cytosolic protein complexes called inflammasomes, assembled by NLRP, activate proinflammatory caspase 1 and 11, which ultimately produce IL-1β and IL-18 or induce cell death. IL-1 serves as an initiator for the recruitment of immune cells and the inflammatory response. Systemic vasculitis, such as Behcet disease, may be related to IL-1 polymorphism, and the expression of NLRP3. Coronary arteritis in KD is associated with an innate immune response, including IL-1. The suggested evidence of innate immunity in KD is related to increased neutrophils and monocytes, high levels of γδT cells, macrophage infiltration in coronary arteries and skin, elevated DAMPs such as S100 or HMGB1, and is sometimes associated with hyperactive innate immunity. The gene of the IL-1 pathway may be related to IVIG-resistant KD, and a clinical trial with IL-1 antagonist is currently ongoing. Adjunctive therapy in KD consists of various strategies, including second IVIG, steroids, and TNF inhibitors. The rationale for adjunctive therapy is based on immune hyperactivation with hypercytokinemia or immune modulation. Further efforts are needed to understand innate immunity and KD, especially in IVIG-resistant cases.

Pediatric-Onset Chronic Inflammatory Demyelinating Polyneuropathy: A Multicenter Study

BackgroundTo evaluate the clinical features, demographic features, and treatment modalities of pediatric-onset chronic inflammatory demyelinating polyneuropathy (CIDP) in Turkey. MethodsThe clinical data of patients between January 2010 and December 2021 were reviewed retrospectively. The patients were evaluated according to the Joint Task Force of the European Federation of Neurological Societies and the Peripheral Nerve Society Guideline on the management of CIDP (2021). In addition, patients with typical CIDP were divided into two groups according to the first-line treatment modalities (group 1: IVIg only, group 2: IVIg + steroid). The patients were further divided into two separate groups based on their magnetic resonance imaging (MRI) characteristics. ResultsA total of 43 patients, 22 (51.2%) males and 21 (48.8%) females, were included in the study. There was a significant difference between pretreatment and post-treatment modified Rankin scale (mRS) scores (P < 0.05) of all patients. First-line treatments include intravenous immunoglobulin (IVIg) (n = 19, 44.2%), IVIg + steroids (n = 20, 46.5%), steroids (n = 1, 2.3%), IVIg + steroids + plasmapheresis (n = 1, 2.3%), and IVIg + plasmapheresis (n = 1, 2.3%). Alternative agent therapy consisted of azathioprine (n = 5), rituximab (n = 1), and azathioprine + mycophenolate mofetil + methotrexate (n = 1). There was no difference between the pretreatment and post-treatment mRS scores of groups 1 and 2 (P > 0.05); however, a significant decrease was found in the mRS scores of both groups with treatment (P < 0.05). The patients with abnormal MRI had significantly higher pretreatment mRS scores compared with the group with normal MRI (P < 0.05). ConclusionsThis multicenter study demonstrated that first-line immunotherapy modalities (IVIg vs IVIg + steroids) had equal efficacy for the treatment of patients with CIDP. We also determined that MRI features might be associated with profound clinical features, but did not affect treatment response.

Clinical profile and outcomes of multisystem inflammatory syndrome in children associated with COVID-19 virus after surgery for congenital heart defects.

To study the clinical presentation, laboratory profile, echocardiographic details, management, and outcomes of children who were diagnosed to have multisystem inflammatory syndrome in children (MIS-C) in the immediate postoperative period after surgery for congenital heart defects (CHDs). This is a prospective case-control study that included children diagnosed to have MIS-C in the postoperative period based on clinical signs, rise in inflammatory markers, and echocardiographic features of ventricular dysfunction or coronary involvement. Management included intravenous immunoglobulin (IVIG), steroids, and antiplatelet medications in addition to routine postoperative care. Out of the 461 children who underwent surgery for CHD between April 1st, 2021, and November 30th, 2021, 18 children were diagnosed with MIS-C. After the initial routine postoperative course, all 18 children had sudden worsening in clinical and laboratory parameters. Other causes such as bacterial infection were ruled out. All of these children had features of MIS-C with ventricular dilatation and dysfunction, coronary artery involvement, and reactive COVID-19 immunoglobulin G antibody. There was a significant improvement in coronary artery dimensions after IVIG administration (P = 0.001). The involvement of the left main coronary artery was associated with significantly increased length of intensive care unit (ICU) and hospital stay (P = 0.019). Mean ICU and hospital stay was prolonged in the MIS-C group. There were two deaths in this group due to severe left ventricular dysfunction. During the pandemic, a proportion of patients undergoing elective cardiac surgery may develop unexpected worsening in clinical status due to MIS-C. A high index of suspicion and prompt treatment with IVIG and steroids may be helpful in improving outcomes.

Role of Immunotherapy in Down Syndrome Disintegrative Disorder (DSDD)

Objective To describe case series of patients with DSDD, successfully treated with immunotherapy including Intravenous Immunoglobulin (IVIG) at a single academic center. Background Down syndrome is the most common chromosomal disorder, and in most cases, is due to trisomy of chromosome 21. DSDD is underrecognized, rapidly progressive neuropsychiatric syndrome with various postulated etiology including psychological stress, primary psychiatric disorder and autoimmunity. Design/Methods Case-1: A 20-year-old fun loving female with trisomy-21 and infantile spasms started having complex partial seizures, hallucinations, speech regression, tics, abnormal head movement and obsessive-compulsive behavior. Case-2: A 20-year-old female cheerleader with trisomy-21, started having rapid regression in language, cognition, social skills and agitation over one year. Case-3: A 22-year-old female dancer with trisomy-21, started having subacute onset depression, hallucinations, sleep changes, anorexia and speech regression over one year. Results Case-1: MRI brain and cerebrospinal fluid (CSF) studies were normal including negative autoimmune encephalitis panel. Serum thyroglobulin and thyroid peroxidase antibody were high. Prolonged oral steroid therapy helped but caused adverse effects. She was able to return to her premorbid baseline with chronic IVIG therapy every 10 weeks. Case-2: MRI brain and CSF were normal. Serum autoimmune encephalitis panel, thyroglobulin antibody and thyroid peroxidase antibody were negative. Pulse IV steroids improved symptoms, however she regressed after stopping steroids. IVIG every 6 weeks along with electroconvulsive therapy improved neurological symptoms. Case-3: MRI brain and EEG were normal. CSF showed elevated white blood cell count. Serum Thyroid antimicrosomal and thyroglobulin antibody were high. One dose of IVIG caused significant improvement in neurological symptoms for 6 weeks. Conclusions DSDD should be considered in patients with down syndrome with rapid regression. It is often associated with positive thyroid peroxidase antibody suggesting immune mediated etiology. Various immunotherapy treatments have been reported in literature including steroid, IVIG, mycophenolate and rituximab with significant improvement in selected patient with autoimmunity.

Timing and Nature of Infections in Multiple Myeloma Patients Treated with Anti-BCMA CAR-T Cells

Introduction: Anti-BCMA CAR-T is a highly effective therapy approved for relapsed/refractory multiple myeloma (MM). Its main toxicities include cytokine release syndrome, neurotoxicity, and cytopenias. Infections are common but not well-studied in this population. In this study, we seek to characterize the timing and nature of infections to better inform appropriate prophylactic measures. Methods: We retrospectively reviewed all MM patients (pts) treated with anti-BCMA CAR-T at Mount Sinai from 2018-2022. Data were collected on baseline characteristics, treatment, disease response, hypogammaglobulinemia (HGG), infections, and prophylactic measures, including intravenous immunoglobulin (IVIg). The study period was from time of CAR-T infusion until progression or death. Chi-squared analysis was used for univariate associations and the Kaplan-Meier method was used for time-to-event calculations. Incidence rates ratios (IRR) were calculated using the exact Poisson method. This study was approved by the Mount Sinai IRB. Results: 80 pts were treated with anti-BCMA CAR-T; the median age was 61 years (range 35-77) and 40% were female. The median time from diagnosis to treatment was 5.1 years, with a median of 5 prior lines of therapy (range 1-18). 71% had high risk cytogenetics, and pts had a median of 2 infections (range 0-8) in the year prior to CAR-T. IVIg was used prophylactically in 95% of pts, usually for at least the first 6 months, and these pts were on IVIg 49% of the total time on study. All patients received prophylaxis for VZV, PCP (if CD4< 200/mm3), and anti-bacterial plus anti-fungal for ANC <500/mm3. Median follow-up was 30.1 months, with ORR of 94%, median PFS of 18.8 months and estimated OS of 70% at 3 years. CRS occurred in 86% (6% grade 3/4), with tocilizumab used in 73% and steroids in 34%. There were a total of 207 infections during 1336 months of follow-up (1.9 per pt-year), including 57 grade 3-5 infections (0.5 per pt-year) among 25 (31%) pts, and 5 (6%) deaths, with infection rates highest in the first 3 months (Figure 1). Deaths from infection occurred at months 3 (bacterial osteomyelitis), 4.6 (COVID-19), 5.3 (bacterial pneumonia), 24.4 (bacterial skin/soft tissue), and 26.4 (fungemia). Infections (all-grade/ grade 3-5) were mostly in the respiratory tract (63%/43%), followed by GI (11%/32%), skin/soft tissue (5%/11%), and bloodstream (5%/21%), and were mostly viral (68%/38%), followed by bacterial (30%/63%) and fungal (2%/5%). Few opportunistic infections occurred, including grade 3 Cryptosporidiosis, grade 3 Citrobacter sedlakii bacteremia, grade 5 Parabacteroides distasonis abscess and osteomyelitis, and grade 5 Saccharomyces fungemia. Of those with follow-up since 2020, 16 (25%) tested positive for SARS-CoV-2, with 4 severe cases including 1 death at 4.6 months (of these, 2 were vaccinated, including the patient who died). Asymptomatic CMV reactivation occurred in 34% and was only treated in 3 patients. 95% developed HGG, with severity difficult to gauge due to routine IVIg use. Immunoglobulin (Ig) recovery occurred at 14.3 months for one uninvolved Ig and 20 months for two uninvolved Igs. Absolute neutrophil count <500/mm3 and absolute lymphocyte count <500/mm3 were each associated with more severe infections (p<0.001). The 26 pts with 1-3 prior lines of therapy (LoT), compared with those with 4+ LoT, had lower overall infection rate (1.68 per pt-year vs 2.42 per pt-year, IRR 0.70, 95% CI [0.51-0.94], p=0.0.013) and grade 3-5 infection rate (0.29 per pt-year vs 0.62 per pt-year, IRR 0.46, 95% CI [0.21-0.91] p=0.016). Discussion: Infections among pts treated with anti-BCMA CAR-T were predominantly viral and occurred in the highest rates in the first 3 months. Neutropenia and lymphopenia, common in the first 3 months, were each associated with more severe infections, emphasizing the need for intensive prophylaxis and close outpatient monitoring during this period. Fungal and other opportunistic infections were rare, although one vaccinated patient died of COVID-19, highlighting the need for passive immunity in this population. Ig recovery occurred at 14.3 months, so the optimal duration of IVIg prophylaxis remains an open question. Of note, pts treated in earlier lines of therapy had significantly fewer infections, including grade 3-5 infections. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

S3324 An Unusual Case of Chronic Rejection Following Liver Transplant Due to Autoantibody Formation During Pregnancy

Introduction: We present a unique case of chronic rejection due to HLA-antibody formation during pregnancy. Case Description/Methods: A 51-year-old female with a history of autoimmune hepatitis received a live donor liver transplant (LDLT) with her husband as the donor in January 2008. HLA crossmatch testing was performed prior to transplant with a negative result. Patient was well overall for 8 years following liver transplant. Moderate elevation of liver enzymes during this period lead to liver biopsies consistent with autoimmune hepatitis but no evidence of acute rejection. Patient became pregnant 8 years after LDLT. She developed moderate-chronic elevation of liver enzymes during pregnancy with the most prominent peaks being 731 IU/L alkaline phosphatase (N: 40-140 IU/L), 200 IU/L aspartate aminotransferase (N: < 35 IU/L), and 160 IU/L alanine aminotransferase (N: < 52 IU/L). In December 2016, the patient had a liver biopsy displaying microvesicular steatosis, endotheliitis, and bile duct damage representative of acute cellular rejection. The patient was placed on quadruple immunosuppression therapy: everolimus, tacrolimus, prednisone, and mycophenolate mofetil. HLA antibody testing was performed at that time to check for donor specific antibodies (DSA). DSA was identified against HLA DQ6, suggesting sensitization to her husband’s HLA antigens that occurred during pregnancy/delivery. Despite extensive treatment, chronic rejection of the liver transplant prevailed with bile duct damage progressing to ductopenia. Additional treatments for her condition included intravenous immunoglobulin (IVIG) therapy every 28 days, with photopheresis and plasmapheresis to reduce leukocytes and immunoglobulins attacking the transplanted liver respectively. However, even with multi-modal therapy, the patient’s condition worsened indicated by a rising MELD (model of end-stage liver disease) score and bilirubin concentration to 8 mg/dL. Discussion: We present a unique case of acute (antibody-mediated) rejection progressing to chronic rejection in a LDLT patient following pregnancy due to sensitization to donor HLA DQ6. Consistent post-transplant HLA antibody testing should be a consideration for LDLT patients for early detection and treatment of DSA before memory B-cell production allows rejection to become chronic. Testing is especially important for monitoring female patients with LDLTs from spouse due to risk of blood exposure during pregnancy.

SARS-CoV-2 and Guillain-Barré Syndrome: Lessons from Viral Infections.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is responsible for the COVID-19 pandemic. COVID-19 has a broad clinical spectrum from asymptomatic patients to multiorgan dysfunction and septic shock. Most of the common symptoms of COVID-19 are classified as respiratory disorders, but some reports show neurological involvements. During the COVID-19 pandemic, a case series of neurological complications, such as Guillain-Barré syndrome (GBS), were reported. GBS is a neuroimmune disorder with acute inflammatory radicular polyneuropathy in different parts of the peripheral nerve. Some studies have reported GBS as an inflammatory neuropathy related to various viral infections, such as cytomegalovirus (CMV), Epstein-Barr Virus (EBV), herpes simplex virus (HSV), human immunodeficiency virus (HIV), influenza, and Zika virus. There are some immunomodulation approaches for the management of GBS. Studies have evaluated the effects of the various therapeutic approaches, including intravenous immunoglobulin (IVIG), plasma exchange (PE), complement inhibitors, and corticosteroids to regulate overactivation of immune responses during GBS in experimental and clinical studies. In this regard, the possible association between GBS and SARS-CoV-2 infection during the outbreak of the current pandemic and also the mentioned therapeutic approaches were reviewed.

Intravenous immunoglobulin in the management and outcome of Stiff‐Person syndrome: A systematic review

Background Stiff Person Syndrome (SPS), a rare immune-mediated neuromuscular disorder, is characterized by rigidity, stiffness, and intermittent spasms of axial and extremity muscles. Various immunotherapies including intravenous immunoglobulin (IVIG) have been used for this autoimmune condition. Here we aim to review the role of IVIG in the treatment of SPS along with its outcome. Methods A systematic literature search of PubMed and Embase was conducted to identify the relevant published articles against the predefined criteria using suitable keywords combinations till September 20, 2021. Data were extracted to produce descriptive information of SPS patients on demographics, diagnostics, treatment with IVIG, and outcome. Results Twelve studies with 216 patients were included in the review and 63.89% of them had classical SPS. Glutamic acid decarboxylase (GAD) autoantibodies were present in 72.68% of the patients and 57.89% in whom electromyography (EMG) was performed had continuous motor activity. IVIG therapy was given to 95 patients in different regimens in various studies and varying scoring systems were used to assess the outcome, and 83.16% showed some form of improvement, 14.74% showed no improvement, while 2.10% worsened. None of the included studies mentioned an adverse effect of IVIG in the patients. Conclusion IVIG may benefit patients with SPS along with other medications. Owing to the rarity of the disease and insufficient studies on the assessment of immunotherapy in SPS, longitudinal studies with a sizable number of patients are required to clarify clinical course, treatment, and outcome in SPS with the use of IVIG.

Cost-effectiveness analysis of infliximab for the treatment of Kawasaki disease refractory to the initial treatment: A retrospective cohort study

BackgroundInfliximab (IFX) treatment is approved in Japan for health insurance coverage in patients with Kawasaki disease (KD). This study aimed to compare the cost-effectiveness of IFX and other therapeutic strategies for KD refractory to initial treatment, including intravenous immunoglobulin (IVIG), steroids, immunosuppressants, and plasma exchange therapy. MethodsThis multicenter, retrospective cohort study utilized data from the public medical insurance system of Japan. The target population included those who received treatment for KD between April 2012 and March 2019. Eligibility criteria were as follows: 1) initial onset of KD, 2) age < 15 years at onset, and 3) administration of 3rd line treatment if the 1st line treatment was IVIG alone or 2nd line treatment if the 1st line treatment was a combination of IVIG and steroids, in accordance with Japanese guidelines (2012). Those with KD-related cardiovascular complications before admission and those with congenital cardiac disease were excluded. The primary outcome was cost-effectiveness, which was calculated based on the number of admission events per annum divided by medical expenses per annum (times/10,000 US dollars). The Wilcoxon test was applied to analyze the difference in cost-effectiveness between patients who had received IFX and those who had not. ResultsAmong 1267 patients with KD, 25 received IFX treatment, while 206 received another treatment after the disease was designated refractory to initial treatment. The frequency of steroid use during initial IVIG treatment (a predictor of severity) was higher in the non-IFX group than in the IFX group (70.4% vs. 32.0%, p < 0.001) but became comparable after propensity-score matching. Our analysis indicated that IFX was more cost-effective than other treatments [1.04 (0.86, 1.34) vs. 1.38 (1.03, 1.79) (times/10,000 US dollars), p = 0.006]. ConclusionsIFX treatment may be more cost-effective than non-IFX treatment for patients with KD that is refractory to initial treatment.

Who Would Have Predicted Multisystem Inflammatory Syndrome in Children?

Purpose of ReviewMultisystem inflammatory disease in children (MIS-C) is a novel post-infectious phenomenon following coronavirus disease-19 (COVID-19). Herein, we present an in-depth review of the latest MIS-C literature related to clinical findings, pathophysiology, imaging and laboratory studies, treatment algorithms, and disease outcomes.Recent FindingsWith its non-specific presentation of fever, gastrointestinal symptoms, cardiovascular injury and shock, systemic inflammation, and Kawasaki disease (KD)-like features, MIS-C can be a diagnostic challenge, overlapping with KD and active COVID-19 infection. However, common laboratory features, imaging findings, and historical clues can lead to accurate diagnosis and allow for appropriate treatment with a variety of immunomodulatory therapies, including intravenous immunoglobulin (IVIG). Aggressive treatment of MIS-C leads to good outcomes. Longitudinal studies continue to illuminate long-term cardiac sequelae and recovery.SummaryMIS-C presents with fever, KD features, gastrointestinal symptoms, cardiac inflammation, and shock. Early recognition and prompt institution of IVIG and glucocorticoids provide for rapid improvement.

Pearls & Oy-sters: Delayed Diagnosis of Acute Motor Axonal Neuropathy With Cardiac Arrest.

We present the case of a 53-year-old female who presented with right lower extremity weakness with preceding systemic symptoms including fever and chest pain. She developed rapid quadriparesis over 24 hours and had ventricular fibrillation with cardiac arrest. Examination demonstrated tetraplegia, facial diplegia with spared extra-ocular movements and areflexia. Electrodiagnostic studies including nerve conduction studies and electromyography were consistent with Acute Motor Axonal Neuropathy (AMAN). This case highlights an atypical asymmetric presentation with initially preserved reflexes, rapid progression and cardiac dysfunction that can occur independent of dysautonomia. Treatment options include intravenous immunoglobulin (IVIg) or plasmapheresis as well as supportive care and long term multidisciplinary rehabilitation and communication strategies.

Intensive Care and Treatment of Severe Guillain-Barré Syndrome.

Guillain–Barré syndrome (GBS) is an acute polyneuropathy mostly characterized by acute flaccid paralysis with or without sensory/autonomous nerve dysfunction. Current immuno therapies including intravenous immunoglobulin (IVIg), plasma exchange (PE), and newly developed biological drugs benefit patients by alleviating hyperreactive immune responses. Up to 30% of patients develop respiratory failure during hospitalization and require mechanical ventilation and intensive care. Immunotherapies, mechanical ventilation, supportive care, and complication management during the intensive care unit (ICU) stay are equally emphasized. The most important aspect of intensive care and treatment of severe GBS, that is, mechanical ventilation, has been extensively reviewed elsewhere. In contrast to immunotherapies, care and treatment of GBS in the ICU setting are largely empirical. In this review, we intend to stress the importance of intensive care and treatment, other than mechanical ventilation in patients with severe GBS. We summarize the up-to-date knowledge of pharmacological therapies and ICU management of patients with severe GBS. We aim to answer some key clinical questions related to the management of severe GBS patients including but not limited to: Is IVIg better than PE or vice versa? Whether combinations of immune therapies benefit more? How about the emerging therapies promising for GBS? When to perform tracheal intubation or tracheostomy? How to provide multidisciplinary supportive care for severe cases? How to avert life-threatening complications in severe cases?

Challenges in Lung Re-Transplantation Following Antibody-Mediated Rejection

<h3>Introduction</h3> Despite lung re-transplantation is becoming more frequent, it continues to present several challenges in regards to the management of immunosuppression and infectious risks. We present a case of invasive aspergillosis that highlights the risks associated with increasing immunosuppression after re-transplantation due to antibody-mediated rejection (AMR). <h3>Case Report</h3> Patient is 30 years-old male who underwent primary bilateral lung transplant in December 2016 due to H1N1 Influenza and respiratory failure. His immunosuppression regimen included tacrolimus, prednisone and mycophenolate mofetil (MMF). In June 2018, the patient developed evidence of a significant lung function decline, multiple de novo donor-specific antibodies, including DR17 and DQ2, and acute cellular rejection along with endarteritis on lung biopsy. His initial AMR therapy protocol included intravenous immunoglobulin (IVIG), plasmapheresis, rabbit anti-thymocyte globulin and carfilzomib. Due to the persistence of circulating DSAs and lung function decline, he received also rituximab and monthly belatacept. Eventually, the patient underwent re-transplantation due to chronic lung allograft dysfunction in June 2019. His immunosuppression included tacrolimus, prednisone, MMF, IVIG and belatacept. In November 2019, the patient developed headache, blurry vision and seizure. He was found to have a left parietal lobe abscess requiring resection (figure 1A). Pathology and cultures confirmed the presence of <i>Aspergillus fumigatus</i>. Belatacept and MMF were held. He was treated successfully for 12 months with voriconazole with resolution of symptoms and improved brain imaging (figure 1B). <h3>Summary</h3> The management of immunosuppression in the setting of AMR and re-transplantaion poses several challenges. However, lung re-transplantation remains an ethically justified measures in highly selected patients.

What is the best treatment approach for sporadic late‐onset nemaline myopathy associated with “monoclonal gammopathy of neurological significance”?

What is the best treatment approach for sporadic late‐onset nemaline myopathy associated with “monoclonal gammopathy of neurological significance”?

Presentation, Treatment Response and Short-Term Outcomes in Paediatric Multisystem Inflammatory Syndrome Temporally Associated with SARS-CoV-2 (PIMS-TS).

The novel Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is the pathogen responsible for Coronavirus Disease 2019 (COVID-19). Whilst most children and young people develop mild symptoms, recent reports suggest a novel paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS). Case definition and classification are preliminary, treatment is empiric and disease-associated outcomes are unclear. Here, we report 29 patients with PIMS-TS who were diagnosed, admitted and treated in the English North West between March and June 2020. Consistent with patterns observed internationally, cases peaked approximately 4 weeks after the initial surge of COVID-19-like symptoms in the UK population. Clinical symptoms included fever (100%), skin rashes (72%), cardiovascular involvement (86%), conjunctivitis (62%) and respiratory involvement (21%). Some patients had clinical features partially resembling Kawasaki disease (KD), toxic shock syndrome and cytokine storm syndrome. Male gender (69%), black, Asian and other minority ethnicities (BAME, 59%) were over-represented. Immune modulating treatment was used in all, including intravenous immunoglobulin (IVIG), corticosteroids and cytokine blockers. Notably, 32% of patients treated with IVIG alone went into remission. The rest required additional treatment, usually corticosteroids, with the exception of two patients who were treated with TNF inhibition and IL-1 blockade, respectively. Another patient received IL-1 inhibition as primary therapy, with associated rapid and sustained remission. Randomized and prospective studies are needed to investigate efficacy and safety of treatment, especially as resources of IVIG may be depleted secondary to high demand during future waves of COVID-19.