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Background: Kawasaki disease (KD) is the most common cause of acquired heart disease in childhood. Coronary artery lesions (CALs) are serious complications of KD that can result in stenosis and thrombosis, but the specific underlying pathogenic mechanisms have not been elucidated. Therefore, exploring biomarkers to help predict early CALs is urgently needed for clinical treatment., Methods: Patients were recruited from three independent cohorts. In the discovery cohort, Data-Independent Acquisition Mass Spectrometry (DIA-MS) was performed to screen plasma proteins from healthy controls (HCs), KD patients prior to intravenous immunoglobulin (IVIG) treatment, and KD patients post-IVIG treatment. KD patients were further divided into KD patients without CALs (nCAL) and with CALs (CALs) groups. Bioinformatic analysis was carried out for the differentially expressed proteins (DEPs) and hub proteins. Candidate proteins were quantified by enzyme-linked immunosorbent assay (ELISA) in the validation cohort 1 and 2. Furthermore, candida albicans cell wall extract (CAWS)-induced KD vasculitis mice and cell models were established to investigate the expression of biomarkers identified in the aforementioned clinical cohort., Results: According to the quantitative proteomics analysis, SERPINE1 was significantly increased in KD patients with CALs. Receiver operating characteristic curves (ROC) revealed that plasma SERPINE1 exhibited greater ability in predicting CALs (AUC = 0.824, P < 0.0001). After IVIG treatment, the concentrations of SERPINE1 in the nCALs group significantly decreased. However, the concentration of SERPINE1 remained persistently elevated in the CALs group. Moreover, the expression of SERPINE1 was significantly upregulated in the heart tissue of KD mice, KD plasma, or tumor necrosis factor-α (TNF-α)-stimulated human coronary artery endothelial cells (HCAECs)., Conclusions: Overall, our results suggest that the plasma concentration of SERPINE1 might serve as a new potential predictive biomarker for CALs in KD patients., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Objective: To analyze the clinical characteristics, treatment, and outcomes of children with complete left bundle branch block (CLBBB) mediated by maternal autoantibodies. Methods: A retrospective analysis was conducted on nine children diagnosed with maternal autoantibody-mediated CLBBB, treated at Beijing Anzhen Hospital and Fujian Provincial Hospital from March 2015 to August 2023. Their clinical characteristics, electrocardiographic and echocardiographic findings before and after treatment were reviewed. Paired sample t -test was used for inter-group comparison. Results: Among the mothers, 6 had positive antinuclear antibodies (ANA), 5 had anti-Sjogren syndrome antigen A antibodies, and 3 had anti-Ro-52 antibodies. The cohort included one female and eight male children, diagnosed with CLBBB at the age of 1 (2, 13) months. The positive autoantibodies in the infants, consisted with maternal antibodies, were detected within the first 3 months of life among 3 cases. Treatments included anti-heart failure therapy, myocardial nutritional support, intravenous immunoglobulin (IVIG) and glucocorticoids. Before treatment, the levels of troponin I (0.175 (0.060, 10.270) μg/L) and N-terminal pro-B-type natriuretic peptide (420 (327, 12 865) ng/L) were elevated, which normalized in most cases after treatment. Post-treatment, the QRS duration significantly shortened compared to pre-treatment ((137±15) vs. (169±25) ms, t =3.76, P <0.001), and the QTc interval significantly decreased ((433±41) vs. (514±27) ms, t =4.95, P =0.001). Before treatment, varying degrees of mitral and tricuspid regurgitation and marked interventricular septal dyskinesia were observed in echocardiography. After treatment, valve regurgitation and ventricular septum motion significantly improved, with a marked increase in left ventricular ejection fraction ((51±13)% vs. (27±6)%, t =-6.66, P <0.001). Conclusions: Maternal autoantibody-mediated CLBBB in children presents with chronic heart failure in infancy. Early treatment with anti-heart failure medications, IVIG and glucocorticoids can improve clinical symptoms.

Mixed cryoglobulinemia is a rare disorder characterized by gangrene, weakness, and arthralgias with variable organ involvement. It is often associated with hepatitis C, HIV, and immunological disorders. Diagnosis is based on clinical features and laboratory testing with serology detecting cryoglobulins. Our patient, a 64-year-old female, presented with weakness, fatigue, and discoloration of her fingers and toes. Physical examination showed upper- and lower-extremity skin changes with dry gangrene. Serology showed a non-hepatitis C status, positive cryoglobulin test with a positive rheumatoid factor, and monoclonal IgM-kappa, confirming the diagnosis of mixed cryoglobulinemia. She was treated with intravenous immunoglobulins, glucocorticoids, multiple cycles of rituximab, cyclophosphamide, and plasma exchange. Following a significant event of exacerbation and relapse requiring a below-knee amputation, this case report aims to raise awareness among clinicians to consider this as a rare cause of gangrene and peripheral neuropathy in an elderly adult.

Introduction: Immune thrombocytopenia (ITP) affecting pregnancy is a diagnostic and often a therapeutic challenge., Areas Covered: We review the current diagnostic criteria for ITP in pregnancy and the potential utility of laboratory tests. We discuss the impact of ITP on pregnancy outcomes and the effects of pregnancy on patients living with chronic ITP.  We describe the criteria for intervention, the evidence supporting first-line treatment approaches and the therapeutic decisions and challenges in cases refractory to steroids and IVIG. We review the evidence supporting the potential use of thrombopoietin receptor agonists for refractory thrombocytopenia. Finally, we describe the diagnostic, prognostic, and treatment approaches to neonatal ITP and considerations regarding breastfeeding. We searched the terms 'immune thrombocytopenia' and 'pregnancy' on PubMed to identify the relevant literature published before 31 December 2023, including within cited references., Expert Opinion: Decreased platelet production may play a role in pregnancy-related ITP exacerbation. Putative mechanisms include placental hormones, such as inhibin. Although IVIG and prednisone usually suffice to achieve hemostasis for delivery, second-line agents are sometimes required to allow for neuraxial anesthesia. There is growing evidence supporting the use of romiplostim during pregnancy; however, its risk of venous thromboembolism warrants further evaluation.

Vaccine challenge responses are an integral component in the diagnostic evaluation of patients with primary antibody deficiency, including Common Variable Immunodeficiency Disorders (CVID). There are no studies of vaccine challenge responses in primary hypogammaglobulinemia patients not accepted for subcutaneous/intravenous immunoglobulin (SCIG/IVIG) replacement compared to those accepted for such treatment. Vaccine challenge responses in patients enrolled in two long-term prospective cohorts, the New Zealand Hypogammaglobulinemia Study (NZHS) and the New Zealand CVID study (NZCS), were compared in this analysis. Almost all patients in the more severely affected SCIG/IVIG treatment group achieved protective antibody levels to tetanus toxoid and H. influenzae type B (HIB). Although there was a highly significant statistical difference in vaccine responses to HIB, tetanus and diphtheria toxoids, there was substantial overlap in both groups. In contrast, there was no significant difference in Pneumococcal Polysaccharide antibody responses to Pneumovax® (PPV23). This analysis illustrates the limitations of evaluating vaccine challenge responses in patients with primary hypogammaglobulinemia to establish the diagnosis of CVID and in making decisions to treat with SCIG/IVIG. The conclusion from this study is that patients with symptoms attributable to primary hypogammaglobulinemia with reduced IgG should not be denied SCIG/IVIG if they have normal vaccine responses., Competing Interests: Declaration of competing interest The authors declare they have no conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: The effectiveness of using only glucocorticoids (GCs) in mild multisystem inflammatory syndrome (MIS-C) cases was compared with combined treatment [GCs + Intravenous immune globulin (IVIG)]., Methods: This retrospective cohort study was conducted between June 1, 2020, and June 1, 2022, in a tertiary care center in Istanbul, Turkey. Clinical and investigational data of the MIS-C patients were analyzed. The patients were divided into two groups: those who received only GCs and those who received the GCs + IVIG combination. The primary outcome focused on assessing the deterioration of the patient's clinical condition, the occurrence of shock, admission to the pediatric intensive care unit (PICU), and the need for additional immunosuppressive medication. Secondary outcomes included evaluating the course of cardiovascular and infection-related complications observed at the one-year follow-up., Results: Ninety-seven MIS-C patients with a median age of 41 (3- 214) months were enrolled. Fifty-six (57.7%) patients were male. All the patients had fever at admission with a temperature of 39 °C (37.5 °C-40.1 °C). Thirty-two patients (33%) had cardiac findings on echocardiography [left ventricular dysfunction (n= 13, 13.5%), coronary artery involvement (n= 11, 11.3%), and dilation of cardiac cavities and/or increased cardiac muscle thickness (n= 8, 8.2%)]. Thirteen patients (13.5%) required intensive care. All patients received GCs [only GCs (group I; n= 65, 67%)], and 32 patients (33%) with severe manifestations and/or cardiac involvement received GCs + IVIG (group II). No mortality was observed. None of the patients had any complaints at the one-year follow-up, and all echocardiography findings were normal., Conclusion: This study provides preliminary evidence that GC monotherapy is a safe treatment alternative for mild MIS-C cases without cardiac involvement., Competing Interests: Declaration of competing interest No conflict of interest was declared by the authors., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The COVID-19 pandemic has become a global health crisis, inflicting substantial morbidity and mortality worldwide. A diverse range of symptoms, including fever, cough, dyspnea, and fatigue, characterizes COVID-19. A cytokine surge can exacerbate the disease's severity. This phenomenon involves an increased immune response, marked by the excessive release of inflammatory cytokines like IL-6, IL-8, TNF-α, and IFNγ, leading to tissue damage and organ dysfunction. Efforts to reduce the cytokine surge and its associated complications have garnered significant attention. Standardized management protocols have incorporated treatment strategies, with corticosteroids, chloroquine, and intravenous immunoglobulin taking the forefront. The recent therapeutic intervention has also assisted in novel strategies like repurposing existing medications and the utilization of in vitro drug screening methods to choose effective molecules against viral infections. Beyond acute management, the significance of comprehensive post-COVID-19 management strategies, like remedial measures including nutritional guidance, multidisciplinary care, and follow-up, has become increasingly evident. As the understanding of COVID-19 pathogenesis deepens, it is becoming increasingly evident that a tailored approach to therapy is imperative. This review focuses on effective treatment measures aimed at mitigating COVID-19 severity and highlights the significance of comprehensive COVID-19 management strategies that show promise in the battle against COVID-19., (© 2023. The Author(s).)

Background and Objective: Autoimmune hemolytic anemia (AIHA) is a rare but important cause of morbidity in pediatric hematology patients. Given its rarity, there is little high-quality evidence on which to base the investigation and management of pediatric AIHA. This scoping review aims to summarize the current evidence and highlight key gaps to inform future studies., Methods: This review searched MEDLINE and the Cochrane CENTRAL Trials Register from 2000 to November 03, 2023. Experimental and observational studies reporting AIHA diagnostic criteria, laboratory workup, or treatment/management in populations with at least 20% of patients ≤18 years were included., Results: Forty-three studies were included, with no randomized controlled trials identified. AIHA diagnostic criteria, diagnostic tests, and treatments were highly variable. First-line treatment approaches include corticosteroids, intravenous immunoglobulin, or both. Approaches to AIHA resistance to first-line therapy were widely variable between studies, but most commonly included rituximab and/or cyclosporine., Conclusions: We identify a heterogenous group of observational studies into this complex, immune-mediated disorder. Standardized definitions and classifications are needed to guide collaborative efforts needed to study this rare disease. The work done by the CEREVANCE group provides an important paradigm for future studies., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Delayed radiation myelopathy (DRM) is a rare yet severe complication of radiotherapy. This condition has a progressive pattern that is often irreversible. Several therapeutic strategies have been introduced to alleviate disease complications, including corticosteroids, hyperbaric oxygen, anticoagulants, and antivascular endothelial growth factor (VEGF) agents. However, despite their beneficial effect, they have not been the definitive treatments for DRM. Here we present the case of a 55-year-old woman with a history of multiple myeloma who developed neurological complications 11 months after radiation therapy. As her radiologic findings demonstrated transverse myelitis, based on the DRM diagnostic criteria, the diagnosis of delayed radiation myelitis was reached. Therefore, methylprednisolone pulse therapy was initiated, resulting in the complete resolution of her neurological symptoms. However, on her follow-up examination, although she did not have new neurological complications, magnetic resonance imaging (MRI) demonstrated a residual enhancement in the thoracic spinal cord area. Hence, due to the possibility of myelitis progression and spinal cord atrophy, intravenous immune globulin (IVIG) was administered, resulting in the resolution of lesion enhancement. Considering this outcome and the immunomodulatory properties of IVIG, it could be regarded as a potential therapeutic option in the case of DRM activity., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Autosomal recessive agammaglobulinemia is a severe primary antibody deficiency disorder typically presenting in infancy. We present a rare case of an 8-year-old boy with AR agammaglobulinemia due to a homozygous splice site variant (c.499-1G > A) in the CD79A gene. Despite monthly intravenous immunoglobulin replacement and prophylactic antibiotics, he developed refractory Helicobacter bilis leg ulcers. Helicobacter species are known for extracellular colonization and are challenging to culture, necessitating molecular diagnostics for identification. The patient required prolonged treatment with intravenous meropenem followed by oral metronidazole and doxycycline for resolution of the ulcers over two years. The patient also exhibited persistent asymptomatic thrombocytopenia, an atypical finding in CD79A mutation cases. This case underscores the importance of genetic diagnosis and targeted antimicrobial therapy in managing rare infections associated with primary immunodeficiencies like autosomal recessive agammaglobulinemia due to CD79A mutation., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

We report a case of a 6-year-old boy with autism spectrum disorder presenting with new-onset squint and 'ptosis' following a recent infection. Clinical examination revealed ataxia and areflexia alongside a dilated pupil poorly reactive to light. Subsequently, his eye movements deteriorated to near-complete ophthalmoplegia at 1-week review. Further investigations inclusive of a magnetic resonance imaging (MRI) brain scan, a computed tomography (CT) venogram and a lumbar puncture were conducted to consider and rule out differential diagnoses. Cerebrospinal fluid analysis revealed an albuminocytologic dissociation. The clinical triad of progressive ophthalmoplegia, areflexia and areflexia alongside albuminocytologic dissociation led to the diagnosis of Miller Fisher syndrome. The patient was commenced on intravenous immunoglobulin and his symptoms showed significant improvement. We use this interesting case to provide context for key learning points about diagnosing Miller Fisher syndrome in children.

Objective: This study aimed to develop a novel scoring system utilizing circulating interleukin (IL) levels to predict resistance to intravenous immunoglobulin (IVIG) in Chinese patients with Kawasaki disease (KD). We further compared this scoring system against six previously established scoring methods to evaluate its predictive performance., Methods: A retrospective analysis was conducted on KD patients who were treated at the cardiovascular medical ward of our institution from January 2020 to December 2022. Six scoring systems (Egami, Formosa, Harada, Kobayashi, Lan and Yang) were analyzed, and a new scoring system was developed based on our data., Results: In our study, 521 KD patients were recruited, 42 of whom (8.06%) were identified as resistant to IVIG. Our study indicated that IVIG-resistant KD patients were at an increased risk for the development of coronary arterial lesions (CALs) (P = 0.001). The evaluation of IVIG resistance using various scoring systems revealed differing levels of sensitivity and specificity, as follows: Egami (38.10% and 88.52%), Formosa (95.24% and 41.13%), Harada (78.57% and 43.22%), Kobayashi (66.67% and 74.95%), Lan (66.67% and 73.49%), and Yang (69.05% and 77.24%). Our novel scoring system utilizing sIL-2R demonstrated the highest sensitivity and specificity of 69.29% and 83.91%, respectively, and calibration curves indicated a favorable predictive accuracy of the model., Conclusion: Our newly developed scoring system utilizing sIL-2R demonstrated superior predictive performance in identifying IVIG resistance among Chinese patients with KD., (© 2024. The Author(s).)

Aims: Early detection and treatment of neurodegenerative Langerhans cell histiocytosis (ND-LCH) have been suggested to prevent neurodegenerative progression. The aim of the study is to validate a standardized multidisciplinary diagnostic work-up to monitor the intravenous immunoglobulins (IVIG) treatment response and the natural course of the disease in untreated patients., Methods: Patients with abnormal somatosensory evoked potentials (SEPs) received monthly 0.5 g/kg IVIG. The diagnostic protocol included structural 3T MRI, neurological examination, brainstem auditory evoked potentials (BAEPs) and SEPs., Results: Twenty-two patients were followed for 5.2 years (median) from the first MRI evidence of ND-LCH. Eleven patients received IVIG for 1.7 years (median). At treatment start neurological examination was abnormal in 10 patients, of whom two had severe clinical impairment and four had abnormal BAEPs. At last follow-up, 1/11 remained stable and 7/11 improved, while worsening of neurological or neurophysiological findings, or both, occurred in 3/11. Risk factors for worsening were a severe clinical or MRI ND-LCH at treatment initiation and prolonged exposure to LCH. Of the 11 untreated patients, none improved and three worsened., Conclusions: Using a standardized diagnostic protocol, we demonstrated that IVIG treatment can lead to clinical stabilization or improvement in all pauci-symptomatic patients with an MRI grading of less than 4., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Trambusti, Barba, Mortilla, Rizzi, Romano, Coniglio, Lucenteforte, Tondo, Guerrini and Sieni.)

Rationale: Kawasaki disease (KD) manifests as an acute, self-limited vasculitis disease that constitutes the primary cause of acquired heart disease in children under 5 years of age. Facial nerve palsy (FNP) is a rare complication associated with coronary artery lesions (CALs) in patients with KD. Patients with KD and FNP usually present atypically, leading to a delayed diagnosis and treatment of KD., Patient Concerns: A 4-month-old boy with fever, left FNP and bilateral conjunctival injection with spontaneous resolution, was admitted to the hospital, received a short course of intravenous dexamethasone, and experienced rapid FNP recovery on the first admission. The patient experienced a resurgence of fever, bilateral conjunctival injection, and right FNP, which led to readmission. Physical examination revealed redness at the site of Bacillus Calmette-Guérin inoculation, reddening of lips, and desquamation of the distal extremities. Echocardiography revealed right-sided CALs., Diagnoses: The patient initially missed KD on the first admission, and was later diagnosed with complete KD with FNP on the second admission., Interventions and Outcomes: After a short course of intravenous dexamethasone, the left FNP resolved quickly. However, right FNP recurred after corticosteroids withdrawal. Meanwhile, more typical symptoms were observed, and KD was diagnosed. Treatment ensued with intravenous immunoglobulin (IVIG), aspirin, and dexamethasone. The patient achieved rapid remission, without recurrence. Echocardiography continued to show normal findings during 1-year follow-up after discharge., Lessons: The clinical symptoms of FNP complicating KD in children are atypical and can easily lead to delayed diagnosis and treatment. FNP in patients with KD may serve as a risk factor for CALs, which are more challenging to resolve than the FNP itself. Adding corticosteroids to IVIG may be recommended to reduce IVIG resistance, decrease the risk of developing CALs, and alleviate CALs., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Competing Interests: Competing interests: None declared.

Purpose: Toxic shock syndrome (TSS) is a rare disease responsible for significant morbidity and mortality. Intravenous immunoglobulin (IG) therapy in paediatric TSS could improve shock and organ failure, but more consistent efficacy and safety data are needed. Our objective was to determine whether a randomised clinical trial (RCT) assessing intravenous IG in TSS in children is feasible., Methods: We performed a multicentre, feasibility, double-blind RCT assessing efficacy of high-dose intravenous IG versus albumin 4% (control group) within the first 12 hours of shock onset. Included patients were aged above 1 month and below 18 years with suspected TSS and septic shock. Feasibility was assessed by measuring inclusion rate, protocol compliance and missing data regarding death and the Pediatric Logistic Organ Dysfunction-2 (PELOD-2) Score. Other secondary clinical outcomes were evaluated during hospital stay, at 60 day and 1 year., Results: 28 patients, admitted in 6 paediatric intensive care units during 36 consecutive months and followed for 1 year, received the allocated treatment: 13 in intravenous IG group, 15 in control group. The median age was 10.6 years and the sex ratio was 1. Inclusion rate was above 50%, protocol deviations were below 30% and missing data regarding death and PELOD-2 Score below 10%. No difference concerning secondary clinical outcomes between groups was observed, and more adverse events were reported in the control group., Conclusion: It seems to be feasible to conduct an RCT assessing intravenous IG efficacy and safety in paediatric TSS but must be realised internationally, with choice of a clinically relevant endpoint and a specific design in order to be realistic., Trial Registration Number: NCT02219165., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a peripheral nerve disorder characterised by weakness and sensory loss. We assessed the neonatal Fc receptor inhibitor rozanolixizumab for CIDP management., Methods: CIDP01 (NCT03861481) was a randomised, subject-blind, investigator-blind, placebo-controlled, phase 2a study. Adults with definite or probable CIDP receiving subcutaneous or intravenous immunoglobulin maintenance therapy were randomised 1:1 to 12 once-weekly subcutaneous infusions of rozanolixizumab 10 mg/kg or placebo, stratified according to previous immunoglobulin administration route. Investigators administering treatment and assessing efficacy, and patients, were blinded. The primary outcome was a change from baseline (CFB) to day 85 in inflammatory Rasch-built Overall Disability Scale (iRODS) score. Eligible patients who completed CIDP01 entered the open-label extension CIDP04 (NCT04051944)., Results: In CIDP01, between 26 March 2019 and 31 March 2021, 34 patients were randomised to rozanolixizumab or placebo (17 (50%) each). No significant difference in CFB to day 85 in iRODS centile score was observed between rozanolixizumab (least squares mean 2.0 (SE 3.2)) and placebo (3.4 (2.6); difference -1.5 (90% CI -7.5 to 4.5)). Overall, 14 (82%) patients receiving rozanolixizumab and 13 (76%) receiving placebo experienced a treatment-emergent adverse event during the treatment period. Across CIDP01 and CIDP04, rozanolixizumab was well tolerated over up to 614 days; no clinically meaningful efficacy results were seen. No deaths occurred., Conclusions: Rozanolixizumab did not show efficacy in patients with CIDP in this study, although this could be due to a relatively high placebo stability rate. Rozanolixizumab was well tolerated over medium-to-long-term weekly use, with an acceptable safety profile., Competing Interests: Competing interests: LQ received research grants from Instituto de Salud Carlos III–Ministry of Economy and Innovation (Spain), CIBERER, GBS-CIDP Foundation International, Grifols, Roche and UCB Pharma; provided expert testimony to Annexon, argenx, Avilar Therapeutics, CSL Behring, Johnson and Johnson, Lundbeck, Lumanity, Merck, Novartis, Octapharma, Roche, Takeda, Sanofi Genzyme and UCB Pharma; serves on the Clinical Trial Steering Committee for Sanofi Genzyme. JDS, TD, TL and THR: report no disclosures relevant to the manuscript. MR served as a consultant and received research support from Alexion and Allergan; received research support from Anelixis Therapeutics, Apellis Pharmaceuticals, Biohaven, Catalyst, MediciNova, Millennium Pharmaceuticals, Momenta (now Johnson and Johnson), Orion, Ra Pharmaceuticals (now UCB Pharma), Seikagaku, Shire Takeda, UCB Pharma and Viela Bio (now Horizon Therapeutics). H-PH received honoraria for serving on steering and data monitoring committees of Bayer Healthcare, Biogen, BMS Celgene, GeNeuro, Merck, Novartis, Octapharma, Roche, TG Therapeutics and UCB Pharma. PK was an employee and shareholder of UCB Pharma during the conduct of the study but is now retired. SS is an employee and shareholder of UCB Pharma. DM was a contractor employed by UCB Pharma during the conduct of this study, but is currently employed by IQVIA. AB was an employee and shareholder of UCB Pharma during the conduct of the study but is currently employed at Otsuka Pharmaceutical Commercialization and Development. A-OC and UM are employees and shareholders of UCB Pharma. FE reports grants from ZonMw (Dutch Governmental Agency) and Prinses Beatrix Spierfonds; he also reports grants from CSL Behring, the GBS-CIDP Foundation, Grifols, Kedrion, Takeda Pharmaceutical Company and Terumo BCT, all outside the submitted work; grants were paid to his institution and were used for investigator-initiated studies within INCbase, an international CIDP registry; in addition, he has received consultancy fees from CSL Behring, Grifols and UCB Pharma, paid to his institution., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Immunoglobulin G subclass deficiencies (IgGsd) comprise a wide clinical spectrum from no symptoms to repeated respiratory infections and risk for the development of lung damage. Our aims were to investigate whether the immunological phenotype of IgGsd patients on and off immunoglobulin replacement therapy (IgRT) was reflected in the clinical features of IgGsd., Method: Thirty patients with IgGsd were included in this prospective study of 18 months of IgRT, followed by 7-18 months of IgRT discontinuation. Blood samples were collected when patients were on and off IgRT and compared with samples from 34 cross-sectional healthy controls. An in-depth lymphocyte phenotyping was performed by flow cytometry and plasma levels of immune checkpoints were assessed., Results: IgG3 subclass deficiency was most common. Patients with IgGsd had decreased levels of activated T cells and B cells and plasma levels of negative immune checkpoint molecules correlated negatively with T cell and B cell activation. The decreased T cell activation level was unaffected by IgRT, while the B cell activation was partly restored. Of note, decreased levels of activated regulatory T cells (Tregs) were found in IgGsd patients and was partly restored during IgRT. The profile of comorbidities did not associate with Treg levels., Discussion: IgGsd is associated with decreased B cell and T cell activation including Tregs, and increased plasma levels of negative immune checkpoint molecules. The consequence of reduced activated Tregs in IgGsd remains unclear. Decreased immune cell activation was partly restored during IgRT, demonstrating that IgRT may contribute to improved immune function in patients with IgGsd., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Wågström, Hjorth, Appelgren, Björkander, Dahle, Nilsson, Nilsdotter-Augustinsson, Ernerudh and Nyström.)

Objective: To assess the effect of intravenous immunoglobulin (IVIG) therapy on unexplained recurrent spontaneous abortion (URSA)., Methods: We retrieved all randomized controlled trials (RCTs) related to the effect of IVIG therapy on URSA in the following databases: PubMed, Embase, Web of Science, and Cochrane Central Register of Controlled Trials before April 30, 2023, according to the PRISMA statement. The therapeutic effect of IVIG was measured by live birth rates. Quality assessment was conducted independently by two reviewers, based on the Newcastle-Ottawa scale. For the meta-analysis, we used odds ratios (random effects model and fixed effects model). The between-study heterogeneity was assessed by the Q test. Publication bias was assessed by funnel plots., Results: A total of 12 studies with 751 participants were included in this meta-analysis. There was no statistical significance [OR = 1.07, 95%CI (0.65, 1.75), P =0.80] between the IVIG group and the non-IVIG group, including low molecular weight heparin (LMWH) plus low-dose aspirin (LDA), intralipid, multivitamins, albumin, and normal saline. A subgroup analysis was conducted according to the different treatment regimens of the non-IVIG group. Compared to the placebo group, including multivitamins, albumin, and saline, the live birth rate of the IVIG group is superior, but there was no statistical significance [OR =1.43, 95%CI (0.99, 2.07), P =0.05]. Another subgroup analysis was performed according to URSA with positive for antiphospholipid antibodies (aPLs). Results showed the live birth rate of IVIG on URSA with positive for aPLs is inferior to that of LMWH plus LDA [OR = 0.25, 95%CI (0.11, 0.55), P =0.0007]., Conclusions: IVIG didn't increase the live birth rate of URSA compared to placebo. Conversely, compared with the IVIG, the LMWH plus LDA treatment schedule can increase the live birth rate of URSA with positive for aPLs., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Ling, Xu, Tian, Chen, Mo and Peng.)

Purpose: Glial fibrillary acidic protein astrocytopathy (GFAP-A) pathogenesis remains uncertain, with potential viral involvement. More clinical cases are needed to deepen our understanding of this disease, along with the exploration of more effective treatment options to provide clinicians with additional choices., Methods: We report a severe case of GFAP-A secondary to EBV infection, characterized predominantly by central respiratory failure. Additionally, we conducted a literature review summarizing the characteristics of GFAP-IgG-positive patients associated with EBV infection., Results: Among the 13 patients identified, fever (92.3%) and headache (84.6%) were the most common initial symptoms, while urinary dysfunction was universally present in all patients. Over half of the patients with altered consciousness required endotracheal intubation (7/11, 63.6%), with only one individual experiencing complete resolution without any residual sequela. Only two patients (16.7%) displayed the classic feature of periventricular enhancement on neuroimaging, whereas T2-FLAIR hyperintensities were more prevalent. All patients tested positive for GFAP-IgG in CSF, and 91.7% (11/12) had detectable serum GFAP-IgG antibodies. Three patients (23.1%) achieved full recovery solely through antiviral therapy. In patients receiving various immunotherapies, 60% (6/10) still had residual sequelae., Conclusion: EBV infection may contribute to the pathogenesis of GFAP-A. GFAP antibody testing is recommended for diagnostic evaluation in cases of central nervous system viral infections presenting with respiratory insufficiency. For severe GFAP-A patients, Protein A immunoadsorption (Protein A IA)., (© 2024. The Author(s).)

Stiff-person syndrome (SPS) usually manifests as an autoimmune neuromuscular disorder characterised by pronounced and advancing rigidity, primarily affecting the trunk and proximal muscles. There are various clinical subtypes like classic SPS (truncal stiffness, generalised rigidity and muscle spasms), partial SPS (stiff-limb syndrome) and uncommon forms including progressive encephalomyelitis with rigidity and myoclonus. Camptocormia, defined as forward flexion of the spine in the upright position that disappears in the supine position, without fixed deformity, has been described only in two cases as an initial presentation of Anti glutamic acid decarboxylase (GAD) autoimmunity. We encountered a young male presenting with a progressive forward-leaning posture and involuntary rhythmic movements in the lower limb. Diagnostic workup included MRI, blood routines, autoimmune screening, genetic testing, lumbar puncture and electromyography. Elevated serum anti-GAD antibody levels, inflammatory CSF and certain other clinical features supported the diagnosis of SPS. Treatment involved benzodiazepines, muscle relaxants and immunotherapy with intravenous immunoglobulin. This case underscores the importance of considering immune-mediated causes, such as SPS, in patients presenting with camptocormia., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Coagulation disorders are common in Kawasaki disease (KD). The main objectives of the present study were to probe the associations of coagulation profiles with clinical classification, IVIG responsiveness, coronary artery abnormalities (CAAs) in the acute episode of KD. A total of 313 KD children were recruited and divided into six subgroups, including complete KD (n = 217), incomplete KD (n = 96), IVIG-responsive KD (n = 293), IVIG-nonresponsive KD (n = 20), coronary artery noninvolvement KD (n = 284) and coronary artery involvement KD (n = 29). Blood samples were collected within 24-h pre-IVIG therapy and 48-h post-IVIG therapy. Coagulation profiles, conventional inflammatory mediators and blood cell counts were detected. Echocardiography was performed during the period from 2- to 14-day post-IVIG infusion. In addition, 315 sex- and age-matched healthy children were enrolled as the controls. (1) Before IVIG therapy, coagulation disorders were more prone to appear in KD patients than in healthy controls, and could be overcome by IVIG therapy. FIB and DD significantly increased in the acute phase of KD, whereas reduced to normal levels after IVIG therapy. (2) PT and APTT were significantly longer in patients with complete KD when compared with their incomplete counterparts after IVIG therapy. (3) The larger δDD, δFDP and the smaller δPT, δINR predicted IVIG nonresponsiveness. (4) The higher δDD and δFDP correlated with a higher risk for CAAs (DD: r = -0.72, FDP: r = -0.54). Coagulation disorders are correlated with complete phenotype, IVIG nonresponsiveness and CAA occurrence in the acute episode of KD, and can be rectified by synergistic effects of IVIG and aspirin., (© 2024. The Author(s).)

Background: Immunoglobulin G replacement therapy (IgRT), intravenous (IV) and subcutaneous (SC) routes, is pivotal in treatment of primary immunodeficiencies (PID). In recent years, facilitated subcutaneous immunoglobulin (fSCIG), a combination of rHuPH20 and 10% IgG has emerged as a delivery method to combine advantages of both IV and SC., Method: In an observational prospective cohort, we investigated patient experience with fSCIG in PID patients from 5 PID centers for up to 12 months. We assessed the efficacy and safety of this treatment with patient/caregiver- and physician-reported indicators. Additionally, we analyzed patient treatment satisfaction (TSQM-9) and quality of life (QoL)., Results: We enrolled 29 patients (22 pediatric and 7 adults; 14 females and 15 males; (median: 15, min-max: 2-40.9 years) who initiated fSCIG as IgRT-naive (n = 1), switched from conventional rapid-push 10% SCIG (n = 6) or IVIG (n = 22). Among the participants, 19 (65%) exhibited antibody deficiencies, 8 (27%) combined immunodeficiencies, and 2 (7%) immune dysregulations. Remarkably, targeted trough immunoglobulin G levels were achieved under all previous IgRTs as well as fSCIG. No severe systemic adverse drug reactions were documented, despite prevalent local (%86.45) and mild systemic (%26.45) adverse reactions were noted with fSCIG. Due to mild systemic symptoms, 2 patients switched from fSCIG to 10% SCIG. The patient satisfaction survey revealed a notable increase at 2-4th (p = 0.102); 5-8th (p = 0.006) and 9-12th (p < 0.001) months compared to the baseline. No significant trends were observed in QoL surveys., Conclusion: fSCIG demonstrates admissable tolerability and efficacy in managing PIDs in addition to notable increase of patients' drug satisfaction with IgRT. The identified benefits support the continuation of this therapy despite the local reactions., (© 2024. The Author(s).)

The catastrophic antiphospholipid syndrome (CAPS) is a rare life-threatening clinical condition that represents the most severe clinical presentation of the antiphospholipid syndrome (APS). It was first described in 1992 in a group of patients that presented with multiorgan involvement and microangiopathic features of APS. Most of the current knowledge of CAPS comes from the analysis of all cases collected at the "CAPS Registry" that was created in 2000 to perform studies on this condition. Most cases are triggered by a prothrombotic situation that leads to a multiorgan thrombosis and a cytokine storm. The analysis of cases included in the "CAPS Registry" has shown that the triple therapy with anticoagulation, glucocorticoids, and plasma exchange and/or intravenous immunoglobulins is associated to a better prognosis of CAPS. The improvement of the knowledge allowed a decrease from the 50% mortality rate reported in the first series to 25-30% in the most recent publications., (Copyright © 2024 Elsevier España, S.L.U. All rights reserved.)

Immune thrombocytopenia is caused by autoantibodies against surface antigens on platelets. Since only about 50 % of cases will allow the identification of glycoprotein-specific antibodies, ITP remains a diagnosis of exclusion. Apart from EDTA-induced pseudo thrombocytopenia, other diseases like secondary thrombocytopenia due to medication, a large number of other disease and hereditary thrombocytopenias must be taken into account. The first-line therapy of ITP includes corticosteroids and intravenous immunoglobulins. The second line consists of thrombopoietin receptor agonists, rituximab, or splenectomy. For further lines of therapy, Fostamatinib and non-steroidal immunosuppressives are available., Competing Interests: Der Autor erklärt, dass keine Interessenskonflikte vorliegen., (Thieme. All rights reserved.)

Evans syndrome is a rare disease marked by a severe clinical course, high relapse rate, infectious and thrombotic complications, and sometimes fatal outcome. Management is highly heterogeneous. There are several case reports but few large retrospective studies and no prospective or randomised trials. Here, we report the results of the first consensus-based expert recommendations aimed at harmonising the diagnosis and management of Evans syndrome in adults. After reviewing the literature, we used a fuzzy Delphi consensus method, with two rounds of a 42-item questionnaire that were scored by a panel of 13 international experts from five countries using a 7-point Likert scale. Panellists were selected by the core panel on the basis of their personal experience and previous publications on Evans syndrome and immune cytopenias; they met virtually throughout 2023. The panellists recommended extensive clinical and laboratory diagnostic tests, including bone marrow evaluation and CT scan, and an aggressive front-line therapy with prednisone (with or without intravenous immunoglobulins), with different treatment durations and tapering for immune thrombocytopenia and autoimmune haemolytic anaemias (AIHAs). Rituximab was strongly recommended as first-line treatment in cold-type AIHA and as second-line treatment in warm-type AIHA and patients with immune thrombocytopenia and antiphospholipid antibodies, previous thrombotic events, or associated lymphoproliferative diseases. However, rituximab was discouraged for patients with immunodeficiency or severe infections, with the same applying to splenectomy. Thrombopoietin receptor agonists were recommended for chronic immune thrombocytopenia and in the case of previous grade 4 infection. Fostamatinib was recommended as third-line or further-line treatment and suggested as second-line therapy for patients with previous thrombotic events. Immunosuppressive agents have been moved to third-line or further-line treatment. The panellists recommended the use of recombinant erythropoietin in AIHA in the case of inadequate reticulocyte counts, use of the complement inhibitor sutimlimab for relapsed cold AIHA, and the combination of rituximab plus bendamustine in Evans syndrome secondary to lymphoproliferative disorders. Finally, recommendations were given for supportive therapy, platelet or red blood cell transfusions, and thrombotic and antibiotic prophylaxis. These consensus-based recommendations should facilitate best practice for diagnosis and management of Evans syndrome in clinical practice., Competing Interests: Declaration of interests WB has received consultancy or advisory board honoraria and speaker's bureau from Alexion, Novartis, Agios, Pfizer, Sanofi, and Sobi. BF has received consultancy or advisory board honoraria and speaker's bureau from Agios, Alexion, Apellis, Janssen, Novartis, Roche, Samsung, Sanofi, and Sobi. HF has received research support from Sanofi and Novartis. AG has received consultancy and research funds from Agios, Bristol Myers Squibb, Novo Nordisk, Saniona, Sanofi, Pharmacosmos, Novartis, AbbVie, and Vertex Pharmaceuticals. TJG-L has received research support from Sobi, Novartis, Amgen, Grifols; speakers bureau from Sobi, Novartis, Amgen, Grifols, argenx, Sanofi, Momenta, and Alpine; and fees for participation in data safety monitoring for Novartis and Alpine. IM has received consultancy honoraria from Alexion, Janssen, Novartis, Apellis, and Sanofi. MaM has received consultancy or speaker's bureau from Alexion, argenx, Sanofi, Novartis, and Sobi. MoM has received consultancy from Gilead, Novartis, AbbVie, and Pfizer. M-EM has received research support, consultancy and speaker's bureau from Amgen, Novartis, Novo Nordisk, Sanofi, Grifols, Sobi, Takeda, and CSL Bering. MN has received speaker fees from Sobi, Novo Nordisk, Amegn, Novartis, Kedrion, Bayer, Takeda, CSL Behring, and Sanofi, and consultancy honoraria from Bayer and CSL Behring. AP has received consultancy or speaker's bureau from Sanofi, Alexion, Novartis, Sobi, Pfizer, Gilead, and Morphosys. SR has received consultancy honoraria from Sanofi, Novartis, and Alexion. NV has received speaker's bureau from Sanofi, Amgen, and Grifols. All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Pediatric immune thrombocytopenia (ITP) is a fairly common bleeding disorder PRESENTING with a decreased number of platelets. The typical clinical presentation involves mild bleeding symptoms with bruising and petechiae and occasional mucosal bleeding. ITP is thought to be an autoimmune disorder and more recently other mechanisms have been described. Most cases resolve spontaneously and can undergo watchful waiting as the platelet count improves. Initially, steroids or intravenous immunoglobulin G (IVIg) can be used to increase platelets. For those cases that do not resolve and become persistent or chronic, there are multiple treatment options, with new agents being studied in adults that will hopefully make it to clinical trials in pediatrics in the future., Competing Interests: Disclosure The authors have nothing to disclose., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Introduction: Small cross-sectional studies and case reports observed improvement after administration of second IVIG dose (SID) amongst Guillain-Barré Syndrome (GBS) patients not responsive to initial IVIG cycle. Nevertheless, recent clinical trial and larger observational studies did not find any positive effects of SID. Instead, an increased risk of thromboembolism and mortality was noted. The conclusions of these studies however were not robust as confounding and selection bias were present., Methodology: Two neurologists conducted the search process (KBA and MBP) using the following terms in Medline: [(" Guillain-Barré Syndrome"[MeSH Terms] or GBS or Acute Motor Axonal Neuropathy or Acute Motor Axonal Neuropathy or Acute Inflammatory Demyelinating Polyneuropathy) AND (Poorly Responsive or Poor Prognosis or Progressive)] AND [("Intravenous Immunoglobulin"[MeSH Terms] or IVIG or IGIV) AND (second dose or retreatment or SID)]., Results: Only 7 articles were included in this review. In terms of primary outcomes, although the cross-sectional study found improvement in GBS DS score at 4 weeks (Median GBS DS: 3 vs 5, p = 0.033) and the 2 case series observed improvement after SID, no significant differences between the control and intervention groups were found in the cohort [Early SIV OR: 0.7 (95% CI 0.16-3.04), Late SIV OR: 0.66 (CI: 0.18-2.5)] and clinical trial studies (Adjusted OR: 1.4 (95% CI:0.6-3.3, p = 0.45). Moreover, 4 patients who died in the clinical trial were from the intervention group., Conclusion: Based on studies with research designs of higher quality, SID is not effective in the management of GBS patients who poorly responded to initial IVIG. Nevertheless, an adequately powered, randomized, double-blinded, placebo-controlled clinical trial, using GBS-DS of 3 and above after first IVIG dose should be done to effectively establish the efficacy and safety of SID as intervention for this cohort of patients., (© 2024. The Author(s) under exclusive licence to Belgian Neurological Society.)

Background and Objectives: In May 2022, the United Kingdom reported the first case of chained transmission of the monkeypox (mpox) virus without any known epidemiological links to west or central Africa. The monthly number of mpox patients currently has passed a peak and is declining globally, and infected patients include both non-vaccinated and vaccinated individuals. Herein, the virus-neutralizing (VN) activity against vaccinia viruses, which are considered to cross-react with the mpox virus, in the intravenous immunoglobulin (IVIG) lots derived from donors, including vaccinated Japanese populations, was evaluated to clarify the status of the Japanese blood donor population., Materials and Methods: VN titres against vaccinia and human mpox viruses in IVIG lots derived from donors in Japan and the United States manufactured between 1999 and 2021 and 1995 and 2001, respectively, were evaluated by neutralization testing., Results: VN titres of IVIG derived from donors in Japan and the United States against vaccinia and mpox viruses showed a slowly decreasing trend between 1999 and 2021., Conclusion: VN titres are expected to decrease in the future since the percentage of vaccinated donors in the donor population seems to have decreased. Therefore, continuous monitoring of VN titres is required., (© 2024 International Society of Blood Transfusion.)

Purpose of Review: Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) are severe cutaneous adverse drug reactions (SCARs) characterized by widespread epithelial detachment and blistering, which affects the skin and mucocutaneous membranes. To date, therapeutic interventions for SJS/TEN have focused on systematic suppression of the inflammatory response using high-dose corticosteroids or intravenous immunoglobulin G (IgG), for example. No targeted therapies for SJS/TEN currently exist., Recent Findings: Though our understanding of the pathogenesis of SJS/TEN has advanced from both an immunological and dermatological perspective, this knowledge is yet to translate into the development of new targeted therapies., Summary: Greater mechanistic insight into SJS/TEN would potentially unlock new opportunities for identifying or repurposing targeted therapies to limit or even prevent epidermal injury and blistering., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

The immune-mediated necrotizing myopathies (IMNM) are autoimmune myositides clinically characterized by proximal predominant weakness and elevated creatine kinase (CK). They may be associated with autoantibodies (anti-HMGCR, anti-SRP), triggered by statin use (e.g., anti-HMGCR myopathy), associated with cancer, or may be idiopathic. Immunotherapy is required to improve strength and decrease the CK level, but no therapies are currently approved by the U.S. Food and Drug Administration for the treatment of IMNM. The optimal treatment strategy for IMNM is currently unknown and wide practice variation exists in the management of this condition. However, observational studies and expert opinion suggest that certain therapies may be more effective for the different serological subtypes of IMNM. HMGCR IMNM often responds favorably to intravenous immunoglobulin (IVIG) even as monotherapy. Signal recognition peptide and seronegative IMNM typically require combination immunotherapy, most often consisting of an oral immunosuppressant, corticosteroids, and IVIG or rituximab. Patients often remain on immunotherapy for years and relapse is common during tapering of immunotherapy. Further studies are needed to guide the optimal management of these patients., (© 2024 by the American Association of Neuromuscular & Electrodiagnostic Medicine, Inc. All rights reserved.)

Purpose: The purpose of this study was to investigate the dynamic changes in serum (1-3)-β-D-glucan (BDG) caused by intravenous immunoglobulins (IVIG) infusion in adults., Methods: This study included patients who received IVIG infusion from October 2021 to October 2022 during hospitalization. We randomly examined two IVIG samples for every patient. Serum samples were collected at nine time points: before (Tpre), immediately (T1-0), 6h (T1-1) and 12h (T1-2) later on the first day; immediately (T2-0) and six hours later (T2-1) on the second day during IVIG infusion, and within three days after IVIG infusion (Ta1, Ta2, and Ta3, respectively). The Friedman test was used for statistical analysis., Results: A total of 159 serum BDG from 19 patients were included in the analysis. The BDG content of IVIG ranged from 249 pg/ml to 4812 pg/ml. Patients had significantly elevated serum BDG on T1-0 (176 (113, 291) pg/ml, p = 0.002) and Ta1 (310 (199, 470) pg/ml, p < 0.001), compared with Tpre (41 (38, 65) pg/ml). The increments of serum BDG (ΔBDG) were associated with BDG concentration of IVIG (Spearman r = 0.59, p = 0.02). Individuals with abnormal renal function indexes showed higher serum ΔBDG values at Ta1 (403 (207, 484) pg/ml) than patients with normal renal function (172 (85, 316) pg/ml, p = 0.036)., Conclusion: Patients who received IVIG had significantly higher serum BDG values. Elevated BDG levels correlate with BDG content of IVIG and abnormal renal function indexes., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to declare., (Copyright © 2024. Published by Elsevier Inc.)

Background: Kawasaki disease (KD) is a vasculitis of unknown etiology in children aged under 5 years. Coronary arterial aneurysm (CAA) is the major complication of KD. It is no longer though to be a self-limiting disease because its cardiovascular sequelae might persist into adulthood. NLRP3 is a key protein of the NLRP3 inflammasome that participates in sterile inflammatory disease. This study investigated the serum levels of NLRP3 in patients with KD at different stages to explore the relationships between serum NLRP3 and clinical parameters., Methods: A total of 247 children enrolled in this study. There were 123 patients in the acute stage of KD, and 93 healthy children made up the healthy control (HC) group. Among the acute KD patients, 52 had coronary arterial aneurysm (KD-CAA) and 71 did not (KD-NCAA). 36 patient samples were collected after IVIG and aspirin treatment. Additionally, 29 patients were in the cardiovascular sequelae stage. Enzyme-linked immunosorbent assay was used to measure serum NLRP3 levels in all subjects., Results: Serum NLRP3 was elevated in the KD group and was even higher in the KD-CAA subgroup than in the KD-NCAA subgroup of acute-stage patients. Serum NLRP3 declined when the patients were treated with IVIG and aspirin, but during the convalescent (coronary sequelae) stage, serum NLRP3 re-increased. Serum NLRP3 was higher in the ≥ 6-mm-coronary-arterial-diameter group than that the < 6-mm-diameter group. The ROC curve of serum NLRP3 indicated its utility in the prediction of both KD and KD-CAA., Conclusions: NLRP3 may be involved in the development of KD and CAA in children with KD. Targeting NLRP3 might mitigate CAA, thereby reducing the risk of cardiovascular events in adulthood., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Competing Interests: The authors have no funding or conflicts of interest to disclose.

A 40-year-old man who attended the emergency department with a scotoma in right eye. He mentioned hearing difficulties and headache for months and he had sensory and motor deficits in the previous days. In the ophthalmic examination, the right eye had areas of arterial occlusion. MRI revealed hyperintense lesions. The patient was diagnosed with Susac syndrome. He was treated with systemic steroids, however, it was not enough to control the condition. Rituximab and intravenous immunoglobulins were added, which allowed the improvement of neurological symptoms, but the alteration of the visual field and the hearing defect did not recover. Early diagnosis of this pathology is essential, since delaying treatment can cause irreversible consequences. Sometimes it is difficult given the wide variety of symptoms and the course of the disease. Ocular manifestations may raise suspicion when the general symptoms are nonspecific., (Copyright © 2024 Sociedad Española de Oftalmología. Published by Elsevier España, S.L.U. All rights reserved.)

Guillain-Barré syndrome (GBS) is a potentially devastating yet treatable disorder. A classically postinfectious, immune-mediated, monophasic polyradiculoneuropathy, it is the leading global cause of acquired neuromuscular paralysis. In most cases, the immunopathological process driving nerve injury is ill-defined. Diagnosis of GBS relies on clinical features, supported by laboratory findings and electrophysiology. Although previously divided into primary demyelinating or axonal variants, this dichotomy is increasingly challenged, and is not endorsed by the recent European Academy of Neurology (EAN)/Peripheral Nerve Society (PNS) guidelines. Intravenous immunoglobulin and plasma exchange remain the primary modalities of treatment, regardless of the electrophysiological subtype. Most patients recover, but approximately one-third require mechanical ventilation, and 5% die. Disease activity and treatment response are currently monitored through interval neurological examination and outcome measures, and the potential role of fluid biomarkers is under ongoing scrutiny. Novel potential therapies for GBS are being explored but none have yet modified clinical practice. This review provides a comprehensive update on the pathological and clinical aspects of GBS for clinicians and scientists., (© 2024 The Author(s). European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Objectives: Idiopathic inflammatory myopathies (IIMs) are heterogeneous diseases characterized by skeletal muscle inflammation associated with cutaneous, pulmonary and/or other visceral organ involvement. IVIG has been recommended as an adjunct therapy for IIM patients refractory to conventional therapy. However, IVIG has high resource needs and increased risk of adverse reactions. Subcutaneous immunoglobulin (SCIG) therapy has been used as an alternative to IVIG in primary immunodeficiencies and neuroinflammatory disorders. We assessed the satisfaction, patient preference and effectiveness in IIM patients who transitioned from IVIG to SCIG., Methods: We retrospectively reviewed consecutive 20 patients with IIM who were transitioned from IVIG to SCIG therapy for >12 months. Patient preference between IVIG and SCIG was surveyed using a questionnaire previously used in studies of neuroinflammatory conditions. In addition, disease flares, changes in immunosuppression, cumulative prednisone doses and global disease activity were evaluated using the Myositis Intention to Treat Index (MITAX) 12 months pre- and post-SCIG initiation., Results: Most patients (78.9%) preferred SCIG over IVIG and preferred home-based therapies to hospital-based therapies. There was no significant difference in global disease activity (MITAX 3.31 vs 3.02) or in cumulative steroid doses 12 months pre- or post-SCIG initiation. Three patients experienced disease flares, five escalated in immunosuppression, while four patients deescalated in immunosuppressive medications., Conclusions: SCIG is preferred by most patients over IVIG without a substantial increased disease activity or need for additional CS. Future cost-effectiveness studies may provide an additional rationale for utilizing SCIG over IVIG for maintenance therapy for IIM., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

The management of persistent symptomatic coronavirus disease 2019 (COVID-19) infections in immunocompromised patients remains unclear. Here, we present the first case of successful antiviral therapy (nirmatrelvir/ritonavir and remdesivir) in combination with intravenous immunoglobulin (IVIg) in a patient who had received CD20 depleting therapy for follicular lymphoma and experienced recurrent COVID-19 relapses. After the patient received IVIg treatment, the viral load decreased without recurrence. Subsequently, it was found that the anti-spike antibody titer in the administered immunoglobulin was high at 9528.0 binding antibody units/mL. Our case highlights the potential of combination therapy with selective IVIg and antiviral drugs for relapsed immunocompromised COVID-19 patients who have received CD20 depleting therapy., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Infection Prevention and Control. Published by Elsevier Ltd. All rights reserved.)

Competing Interests: Disclosures The authors have no conflicts of interest to report.

Background: Severe post-vaccination neurological complications are rare. Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) is an immune-mediated polyneuropathy affecting the peripheral nerve roots, which is not well described as a post-vaccination side effect. Here, we present a rare complication of vaccination against SARS-CoV-2, reaching a diagnosis of CIDP., Case Presentation: A 67-year-old diabetic male presented with lower extremity paresthesia and weakness following the third dose of the Sinopharm (BBIBP-CorV) vaccine. Despite initial dismissal as a diabetic complication, symptoms escalated, affecting all extremities. Electromyography study revealed abnormal spontaneous activity with chronic reinnervation changes, which was more significant in the lower extremities. Based on the clinical course, radiographic imaging, and laboratory data, a diagnosis of CIDP with severe axonal demyelinating features was established. Treatment with intravenous immunoglobulin (IVIg), prednisolone, and azathioprine resulted in marked improvement of the upper extremities but limited recovery in distal lower extremity muscles., Conclusion: Although CIDP is a rare complication following COVID-19 vaccination, it should be considered in the differential diagnosis. Timely diagnosis of vaccine-induced CIDP is challenging, and any delay can adversely affect treatment response in affected patients., (© 2024. The Author(s).)

Introduction: X-linked agammaglobulinemia (XLA) is a humoral immunodeficiency disorder characterized by recurrent infections, severe hypogammaglobulinemia, and a deficiency of circulating B cells. While the hallmark clinical manifestations of XLA typically include the respiratory, dermatological, and gastrointestinal systems, renal involvement is infrequent. In this article, we report two cases of XLA with concurrent renal disease, supplemented with a review of documented cases., Case Description: The two cases described involve twin brothers, both presenting with respiratory tract infections and renal manifestations. Subsequent genetic testing confirmed the diagnosis of XLA. The younger brother exhibited improvement following intravenous immunoglobulin (IVIG) therapy and anti-infection treatment. Due to financial constraints, the older brother received only anti-infection and symptomatic treatments. Seven months after discharge, the older brother developed nephritis. However, he showed improvement following IVIG treatment., Conclusion: Immune profiling and genetic testing should be considered in male children with recurrent infections to facilitate the effective diagnosis of XLA. Regular monitoring is also imperative to detect and treat immune-mediated renal diseases in patients with XLA., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Wan, Cao, Zou, Bai, Shi and Jiang.)

This case report details a female patient with multiple sclerosis in her 30s, who experienced a significant fingolimod rebound syndrome post partum, characterised by worsening neurological symptoms and severe demyelinating lesions. Traditional treatments, including steroids and plasmapheresis, were ineffective. However, the introduction of intravenous immunoglobulin (IVIG) led to remarkable improvement in her symptoms and disability status. This case highlights the complex immunological changes associated with fingolimod cessation and underscores IVIG's potential as a valuable treatment in managing such rebounds., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Fetal autoimmune atrioventricular block (AVB) is a rare but potentially life-threatening condition. It results from the passage of maternal anti-SSA/Ro or Anti SSB/La auto-antibodies into the fetal circulation, leading to inflammation and fibrosis of the AV node and often to irreversible damage. Besides AVB, these antibodies can also cause cardiomyopathies, but there is no evidence linking them to tachyarrhythmias. We present the case of a patient with significant risk factors for fetal AVB: a prior history of hydrops fetalis , high anti-SSA/Ro antibody levels and hypothyroidism. In this case, the use of dexamethasone and intravenous immunoglobulin may have contributed to reversing the first-degree atrioventricular block detected at 19 weeks of gestation. Additionally, at 21 weeks, the fetus developed a tachyarrhythmia that needed treatment with flecainide. Soon after the birth, the newborn underwent ECG Holter and Wolff-Parkinson-White Syndrome (WPWS) was diagnosed. To our knowledge, the coexistence of fetal AVB and WPWS has never been described., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Chícharo, Rebelo, Lopes, Saavedra, Paramés, Araújo, Cruz-Machado, Pinto and Capela.)

Background: Guillain-Barré syndrome (GBS) is a polyradiculoneuropathy mediated by the immune system and is the primary reason for acute flaccid paralysis. Intravenous immunoglobulin (IVIg) is a recognized immunotherapeutic drug that can accelerate recovery from GBS. Limited literature exists concerning cerebral infarction complications with IVIg following its use in the treatment of GBS., Case Presentation: A patient was diagnosed with the acute inflammatory demyelinating polyradiculoneuropathy subtype of GBS, while another patient was diagnosed with the acute bulbar palsy variant of GBS 2 years prior and experienced a relapse of GBS. Both patients received immunoglobulin therapy, during which multiple acute cerebral infarctions were detected using magnetic resonance imaging. Both patients had a history of coronary artery atherosclerotic heart disease and vertebral artery stenosis, and D-dimer and fibrinogen degradation products were significantly elevated after immunoglobulin therapy., Conclusions: The risk of cerebral infarction associated with IVIg is generally low in patients with different GBS variants. Nevertheless, the occurrence of cerebral infarction associated with IVIg might not be insignificant in older patients with vascular risk factors and should be carefully monitored., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Wang, Feng, Liu, Tao, Bi and Hou.)

Background: Kawasaki disease (KD) has been considered as the most common required pediatric cardiovascular diseases among the world. However, the molecular mechanisms of KD were not fully underlined, leading to a confused situation in disease management and providing precious prognosis prediction. The disorders of gut microbiome had been identified among several cardiovascular diseases and inflammation conditions. Therefore, it is urgent to elucidate the characteristics of gut microbiome in KD and demonstrate its potential role in regulating intravenous immunoglobulin (IVIG) resistance and coronary artery injuries., Methods: A total of 96 KD children and 62 controls were enrolled in the study. One hundred forty fecal samples had been harvested from KD patients, including individuals before or after IVIG treatment, with or without early coronary artery lesions and IVIG resistance. Fecal samples had been collected before and after IVIG administration and stored at -80°C. Then, metagenomic analysis had been done using Illumina NovaSeq 6000 platform. After that, the different strains and functional differences among comparisons were identified., Results: First, significant changes had been observed between KD and their controls. We found that the decrease of Akkermansia muciniphila , Faecalibacterium prausnitzii , Bacteroides uniformis , and Bacteroides ovatus and the increase of pathogenic bacteria Finegoldia magna , Abiotrophia defectiva , and Anaerococcus prevotii perhaps closely related to the incidence of KD. Then, metagenomic and responding functional analysis demonstrated that short-chain fatty acid pathways and related strains were associated with different outcomes of therapeutic efficacies. Among them, the reduction of Bacteroides thetaiotaomicron , the enrichment of Enterococcus faecalis and antibiotic resistance genes had been found to be involved in IVIG resistance of KD. Moreover, our data also revealed several potential pathogenetic microbiome of that KD patients with coronary artery lesions., Conclusion: These results strongly proved that distinct changes in the gut microbiome of KD and the dysfunction of gut microbiomes should be responsible for the pathogenesis of KD and significantly impact the prognosis of KD., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Han, Liu, Lan, Hua, Fan and Li.)

Background and Objectives: Immune thrombocytopenia (ITP) is an autoimmune disease characterized by the autoantibody-mediated destruction of platelets. The treatment of ITP aims to maintain a sufficient platelet count to prevent bleeding. First-line treatment options include corticosteroids and intravenous immunoglobulin (IVIg), while second-line treatments include splenectomy, rituximab and other immunosuppressive agents, and thrombopoietin (TPO) receptor agonists. This study aims to discuss the treatment methods and results from 100 patients with ITP at the Muğla Training and Research Hospital through a pharmacological approach. Materials and Methods: Demographic characteristics, clinical findings, bone marrow aspiration and biopsy results, and treatments and treatment responses at the time of diagnosis of the 100 patients with ITP who were treated and followed up in the period 2015-2023 were evaluated retrospectively. Results: In the third month after treatment, the overall response percentage was 100% in patients who received steroids only and 88% in patients who received IVIg treatment alone or in combination with steroids ( p > 0.05). The most preferred second-line treatments were splenectomy (41%), eltrombopag (26%), and rituximab (10%). Bone marrow biopsy was performed in 54% of patients, where 35.1% showed increased megakaryocytes, 44.4% adequate megakaryocytes, and 14.8% decreased megakaryocytes. It is noted that eltrombopag and rituximab, in particular, yield higher complete remission rates than immunosuppressive drugs. Conclusions: Considering the side effects of immunosuppressive medications, IVIg, splenectomy, and steroid therapy, the use of new agents such as eltrombopag, which are easily tolerated and have a lower risk of side effects, is expected to increase.