Severe papilloedema with vision loss secondary to Guillain-Barré syndrome.

We discuss a patient who presented with bilateral VI and VII cranial nerve palsies, symmetric upper and lower limb weakness and areflexia, 2 weeks following an flu-like illness. At presentation, there was no papilloedema, and her visual function was normal. Cerebrospinal fluid analysis and electrophysiology supported the diagnosis of Guillain-Barré Syndrome (GBS). She received intravenous immunoglobulins. She subsequently developed headaches and vision loss. Funduscopy demonstrated severe papilloedema with visual acuity of 6/18 right eye, 6/12 left eye with bitemporal visual field depression. Lumbar puncture revealed elevated opening pressure with high protein and normal cell count. She received acetazolamide. There was resolution of papilloedema and normal visual function at 3 months. Of note, the patient's body mass index was 17 kg/m2Our case highlights the rare occurrence of papilloedema in GBS, reiterating the importance of performing funduscopy on patients with any neurological diagnosis. Early detection and prompt management of papilloedema can prevent permanent vision loss.

Kawasaki disease in Kenya and review of the African literature.

BACKGROUND: Kawasaki disease has been described across the globe, although publications from Africa are limited. To our knowledge, there are no publications on Kawasaki disease from Kenya, which triggered this report. METHODS: A retrospective cross-sectional study was undertaken to identify in-patients with a discharge diagnosis of Kawasaki disease, over 2 different 5-year periods, at two pediatric hospitals in Nairobi, Kenya. We reviewed the medical records of all patients and report their clinical findings, diagnostic workup and treatment. In addition, we undertook a detailed review of the literature. RESULTS: Twenty-three patients with Kawasaki disease were identified, of those 12 (52.2%) had incomplete disease. The mean age was 2.3 years (SD+/-2.2) (range 0.3-10.3) with a male to female ratio of 1:1. The mean duration of fever at diagnosis was 8.3 days (SD+/-4.7) (range 2-20). Oral changes were the most common clinical feature and conjunctivitis the least common. Thrombocytosis at diagnosis was seen in 52% (12/23). Twenty-one patients (91.3%) were treated with intravenous immunoglobulin and all except 1 received aspirin. Baseline echocardiograms were performed in 95.7% (22/23) and found to be abnormal in 3 (13.6%). Follow-up data was limited. Our literature review identified 79 publications with documented cases of Kawasaki disease in children from 22 countries across the African continent with a total of 1115 patients including those from this report. Only 153 reported cases, or 13.7%, are from sub-Saharan Africa. CONCLUSIONS: This is the first publication on Kawasaki disease from Kenya and one of the largest reports from sub-Saharan Africa. It is the first to have a complete review of the number of published cases from the African continent. Challenges in the diagnosis and management of Kawasaki disease in many African countries include disease awareness, infectious confounders, access and cost of intravenous immunoglobulin, access to pediatric echocardiography and follow-up. Increasing awareness and health care resources are important for improving outcomes of Kawasaki disease in Africa.

Functional and Cutaneous Treatment Outcomes With Intravenous Immunoglobulin for Eosinophilic Fasciitis: A Retrospective Study.

BACKGROUND: Eosinophilic fasciitis (EF) is a rare subtype of deep morphea with an elevated risk of functional impairment. No treatment algorithm has been established for adults with EF refractory to traditional corticosteroid or immunomodulatory treatments. Research on cutaneous and functional outcomes of alternative therapies, such as intravenous immunoglobulin (IVIG), remains scarce.  Objective: To describe the functional and cutaneous outcomes associated with IVIG in adults with treatment-refractory EF at a tertiary referral center. METHODS: We performed a retrospective chart review of 18 consecutive patients with EF identified through a billing code search seen within the UCSF Department of Dermatology between 2015 and 2022.  Results: Seven patients (41.2%) underwent at least one course of intravenous immunoglobulins (IVIG) during the study period. Of 6 patients with available follow-up data, 5 patients (83.3%) achieved both sustained cutaneous and functional improvement. In the IVIG cohort, 1 patient (16.7%) achieved complete response with relapse, 4 (66.7%) were partial responders, and 1 (16.7%) was a non-responder who required treatment with mepolizumab. CONCLUSION: Adverse effects of IVIG included headaches in 1 patient (14.3%) and rash in 2 patients (28.6%). There were no reported veno-occlusive or thromboembolic events associated with IVIG.  J Drugs Dermatol. 2024;23(4):8017.    doi:10.36849/JDD.8017e.

Transverse spinal cord infarction following immunoglobulin treatment in a patient with exfoliative dermatitis: A case report.

RATIONALE: Transverse spinal cord infarction (SCI) is rare but highly disabling. Aortic thrombosis was described as one of the most common etiologies. Thromboembolic complications associated with intravenous immunoglobulin (IVIG) have been reported. PATIENT CONCERNS: A previously well, 64-year-old man who was given the treatment of IVIG (0.4 g/kg/d for 5 days) for exfoliative dermatitis 2 weeks before, progressively developed flaccid paraplegia of lower extremities, loss of all sensations below T3 level and urinary incontinence within 50 minutes. DIAGNOSES: A diagnosis of SCI and pulmonary embolism was made. IVIG was considered the possible cause. INTERVENTIONS: Anticoagulation treatment and continuous rehabilitation were administered. OUTCOMES: The neurologic deficiency of the patient was partially improved at the 3-year follow-up. LESSONS: The rapid development of severe deficits within 4 hours mostly contributes to the diagnosis of SCI. Heightened awareness of possible thrombotic events is encouraged for a month-long period following IVIG therapy.

C-reactive protein to albumin ratio as a prognostic tool for predicting intravenous immunoglobulin resistance in children with kawasaki disease: a systematic review of cohort studies.

BACKGROUND: Intravenous immunoglobulin (IVIG) is the primary treatment for Kawasaki disease (KD). However, 10-20% of KD patients show no response to IVIG treatment, making the early prediction of IVIG resistance a key focus of KD research. Our aim is to explore the application of the C-reactive protein to albumin ratio (CAR) for predicting IVIG resistance in children with KD through meta-analysis. METHODS: Cochrane Library, PubMed, MEDLINE, EMbase, CNKI, WanFang, the Chinese Biomedical Database, and CQVIP were searched up to November 2023 for cohort studies on predicting IVIG-resistant KD using the CAR. Articles were selected based on pre-established inclusion and exclusion criteria after extracting literature data and assessing them using the QUADAS-2.0 tool for evaluating the accuracy of diagnostic tests. Stata 15.0 software was used for meta-analysis. RESULTS: Four Chinese and English literature reports were included in this meta-analysis. The results revealed the presence of a threshold effect and high heterogeneity among the included studies. The combined sensitivity for CAR predicting IVIG-resistant KD was calculated as 0.65 (95% CI 0.58-0.72), specificity as 0.71 (95% CI 0.57-0.81), and the area under the curve (AUC) as 0.70 (95% CI 0.66-0.74) using the random-effects model. The combined positive likelihood ratio was 2.22 (95% CI 1.35-3.65), the combined negative likelihood ratio was 0.49 (95% CI 0.35-0.69), and the diagnostic odds ratio was 5 (95% CI 2-10). CONCLUSION: CAR is an auxiliary predictive indicator with moderate diagnostic value that provides guidance in the early treatment of the disease, demonstrating a certain predictive value that warrants further investigation. However, CAR cannot yet be considered as a definitive diagnostic or exclusionary marker for IVIG-resistant KD. Therefore, multi-center, large sample, and high-quality long-term follow-up trials are warranted to confirm the current findings.

Dynamics and prognostic value of serum neurofilament light chain in Guillain-Barré syndrome.

BACKGROUND: Neurofilament light chain (NfL) is a biomarker for axonal damage in several neurological disorders. We studied the longitudinal changes in serum NfL in patients with Guillain-Barré syndrome (GBS) in relation to disease severity, electrophysiological subtype, treatment response, and prognosis. METHODS: We included patients with GBS who participated in a double-blind, randomised, placebo-controlled trial that evaluated the effects of a second course of intravenous immunoglobulin (IVIg) on clinical outcomes. Serum NfL levels were measured before initiation of treatment and at one, two, four, and twelve weeks using a Simoa HD-X Analyzer. Serum NfL dynamics were analysed using linear mixed-effects models. Logistic regression was employed to determine the associations of serum NfL with clinical outcome and the prognostic value of serum NfL after correcting for known prognostic markers included in the modified Erasmus GBS Outcome Score (mEGOS). FINDINGS: NfL levels were tested in serum from 281 patients. Serum NfL dynamics were associated with disease severity and electrophysiological subtype. Strong associations were found between high levels of serum NfL at two weeks and inability to walk unaided at four weeks (OR = 1.74, 95% CI = 1.27-2.45), and high serum NfL levels at four weeks and inability to walk unaided at 26 weeks (OR = 2.79, 95% CI = 1.72-4.90). Baseline serum NfL had the most significant prognostic value for ability to walk, independent of predictors included in the mEGOS. The time to regain ability to walk unaided was significantly longer for patients with highest serum NfL levels at baseline (p = 0.0048) and week 2 (p < 0.0001). No differences in serum NfL were observed between patients that received a second IVIg course vs. IVIg and placebo. INTERPRETATION: Serum NfL levels are associated with disease severity, axonal involvement, and poor outcome in GBS. Serum NfL potentially represents a biomarker to monitor neuronal damage in GBS and an intermediate endpoint to evaluate the effects of treatment. FUNDING: Prinses Beatrix Spierfonds W.OR19-24.

NLRC4 methylation and its response to intravenous immunoglobulin therapy in Kawasaki disease: a case control study.

BACKGROUND: Kawasaki disease (KD) is a systemic vasculitis accompanied by many systemic physiological and biochemical changes. Elucidating its molecular mechanisms is crucial for diagnosing and developing effective treatments. NLR Family CARD Domain Containing 4 (NLRC4) encodes the key components of inflammasomes that function as pattern recognition receptors. The purpose of this study was to investigate the potential of NLRC4 methylation as a biomarker for KD. METHODS: In this study, pyrosequencing was utilized to analyze NLRC4 promoter methylation in blood samples from 44 children with initial complete KD and 51 matched healthy controls. Methylation at five CpG sites within the NLRC4 promoter region was evaluated. RESULTS: Compared to controls, NLRC4 methylation significantly decreased in KD patients (CpG1: p = 2.93E-06; CpG2: p = 2.35E-05; CpG3: p = 6.46E-06; CpG4: p = 2.47E-06; CpG5: p = 1.26E-05; average methylation: p = 5.42E-06). These changes were significantly reversed after intravenous immunoglobulin (IVIG) treatment. ROC curve analysis demonstrated remarkable diagnostic capability of mean NLRC4 gene methylation for KD (areas under ROC curve = 0.844, sensitivity = 0.75, p = 9.61E-06, 95% confidence intervals were 0.762-0.926 for mean NLRC4 methylation). In addition, NLRC4 promoter methylation was shown to be significantly negatively correlated with the levels of central granulocyte percentage, age, mean haemoglobin quantity and mean erythrocyte volume. Besides, NLRC4 promoter methylation was positively correlated with lymphocyte percentage, lymphocyte absolute value. CONCLUSIONS: Our work revealed the role of peripheral NLRC4 hypomethylation in KD pathogenesis and IVIG treatment response, could potentially serve as a treatment monitoring biomarker, although its precise functions remain to be elucidated.

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

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

Can low-dose intravenous immunoglobulin be an alternative to high-dose intravenous immunoglobulin in the treatment of children with newly diagnosed immune thrombocytopenia: a systematic review and meta-analysis.

Intravenous immunoglobulin (IVIg) is a first-line treatment for children with newly diagnosed immune thrombocytopenia (ITP). Higher doses of IVIg are associated with a more insupportable financial burden to pediatric patients' families and may produce more adverse reactions. Whether low-dose IVIg (LD-IVIg) can replace high-dose IVIg (HD-IVIg) has yet to be established. We conducted a comprehensive literature search from the establishment of the database to May 1, 2023, and eventually included 22 RCTs and 3 cohort studies compared different dosages of IVIg. A total of 1989 patients were included, with 991 patients in the LD-IVIg group and 998 patients in the HD-IVIg group. Our results showed no significant differences between the two groups in the effective rate (LD-IVIg: 91% vs. HD-IVIg: 93%; RR: 0.99; 95%CI: 0.96-1.02) and the durable remission rate (LD-IVIg: 65% vs. HD-IVIg: 67%; RR: 0.97; 95%CI: 0.89-1.07). Similar results were also found in the time of platelet counts (PC) starting to rise (MD: 0.01, 95%CI: -0.06-0.09), rising to normal (MD: 0.16, 95%CI: -0.03-0.35), and achieving hemostasis (MD: 0.11, 95%CI: -0.02-0.23) between the two groups. Subgroup analysis showed the effective rate of 0.6 g/kg was equal to 1 g/kg subgroup (91%) but higher than 0.8 g/kg subgroup (82%), and a combination with glucocorticoid may contribute to effect enhancement (combined with glucocorticoid: 91% vs. IVIg alone: 86%) whether combined with dexamethasone (92%) or methylprednisolone (91%). Besides, the incidence rate of adverse reactions in the LD-IVIg group (3%) was significantly lower than the HD-IVIg group (6%) (RR: 0.61; 95%CI: 0.38-0.98). So low-dose IVIg (≤ 1 g/kg) is effective, safe, and economical, which can replace high-dose IVIg (2 g/kg) as an initial treatment. This systematic review was registered in PROSPERO (CRD42022384604).

Involvement of IL-17 A/IL-17 Receptor A with Neutrophil Recruitment and the Severity of Coronary Arteritis in Kawasaki Disease.

PURPOSE: To assess the role of the interleukin (IL)-17 A/IL-17 receptor A (IL-17RA) in Kawasaki disease (KD)-related coronary arteritis (CA). METHODS: In human study, the plasma levels of IL-17 A and coronary arteries were concurrently examined in acute KD patients. In vitro responses of human coronary endothelial cells to plasma stimulation were investigated with and without IL-17RA neutralization. A murine model of Lactobacillus casei cell-wall extract (LCWE)-induced CA using wild-type Balb/c and Il17ra-deficient mice were also inspected. RESULTS: The plasma levels of IL-17 A were significantly higher in KD patients before intravenous immunoglobulin therapy, especially in those with coronary artery lesion. The pre-IVIG IL-17 A levels positively correlated with maximal z scores of coronary diameters and plasma-induced endothelial mRNA levels of chemokine (C-X-C motif) ligand-1, IL-8, and IL-17RA. IL-17RA blockade significantly reduced such endothelial upregulations of aforementioned three genes and inducible nitric oxide synthase, and neutrophil transmigration. IL-17RA expression was enhanced on peripheral blood mononuclear cells in pre-IVIG KD patients, and in the aortic rings and spleens of the LCWE-stimulated mice. LCWE-induced CA composed of dual-positive Ly6G- and IL-17 A-stained infiltrates. Il17ra-deficient mice showed reduced CA severity with the fewer number of neutrophils and lower early inducible nitric oxide synthase and chemokine (C-X-C motif) ligand-1 mRNA expressions than Il17ra+/+ littermates, and absent IL-17RA upregulation at aortic roots. CONCLUSION: IL-17 A/IL-17RA axis may play a role in mediating aortic neutrophil chemoattraction, thus contributory to the severity of CA in both humans and mice. These findings may help to develop a new therapeutic strategy toward ameliorating KD-related CA.

Physician awareness and understanding of chronic inflammatory demyelinating polyradiculoneuropathy in Japan: a web-based study.

OBJECTIVES: To investigate potential knowledge gaps between neurologists and non-specialists and identify challenges in the current management of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), with a focus on 'early diagnosis' and 'appropriate treatment' for CIDP. DESIGN: A non-interventional, cross-sectional, web-based quantitative survey of physicians working in healthcare clinics or hospitals in Japan. SETTING: Participants were recruited from the Nikkei Business Publications panel from 18 August to 14 September 2022. PARTICIPANTS: Responses from 360 physicians (120 each of internists, orthopaedists and neurologists) were collected. OUTCOME MEASURES: Responses relating to a CIDP hypothetical case and current understanding were assessed to determine awareness, collaboration preferences and diagnosis and treatment decisions. RESULTS: Understanding of CIDP was 90.8% among neurologists, 10.8% among orthopaedists and 13.3% among internists; >80% of orthopaedists and internists answered that neurologists are preferable for treatment. Diagnostic assessment using a hypothetical case showed 95.0% of neurologists, 74.2% of orthopaedists and 72.5% of internists suspected CIDP. Among orthopaedists and internists suspecting CIDP, >70% considered referring to neurology, while ~10% considered continuing treatment without a referral. Among neurologists, 69.4% chose intravenous immunoglobulin (IVIg) as first-line treatment and determined effectiveness to be ≤3 months. CONCLUSIONS: Orthopaedists and internists had lower CIDP awareness compared with neurologists, which may lead to inadequate referrals to neurology. Evaluation of IVIg effectiveness for maintenance therapy occurred earlier than the guideline recommendations (6-12 months), risking premature discontinuation. Improving CIDP knowledge among orthopaedists and internists is critical for better diagnosis and collaboration with neurologists. Neurologists should consider slow and careful evaluation of IVIg maintenance therapy. TRIAL REGISTRATION NUMBER: UMIN000048516.

Clinical characteristics of Guillain-Barré syndrome in patients with primary Sjögren's syndrome.

To investigate the clinical characteristics of Guillain-Barré syndrome (GBS) in patients with primary Sjögren's syndrome (SS). Records of patients with positive anti-SSA antibodies hospitalized in the Beijing Tiantan Hospital between December 2011 and May 2020 were retrieved. Patients who fulfilled the criteria for diagnosis of GBS and primary SS were included, and their clinical data were analyzed. Among the 785 patients with positive anti-SSA, 52 patients were identified in this study. They were 27 males and 25 females with median age of 59 years old. Besides anti-SSA antibodies, multiple autoantibodies were detected in these patients including antinuclear antibody, anti-Ro52, anti-mitochondrial M2, anti-thyroid peroxidase and anti-thyroglobulin autoantibodies. Preceding infection was reported in 42 patients. Hyporeflexia/areflexia and limbs weakness were the most common manifestation and 35 patients presented cranial nerve injuries. GBS disability score of 3, 4 and 5 was scaled in 28 (53.8%), 15 (28.8%) and 3 (5.8%) patients respectively. Forty-six patients received intravenous immunoglobulin (IVIG) monotherapy, 5 patients were treated by IVIG plus glucocorticoids, and 51 patients improved during hospitalization. The frequency of male gender among the patients with both GBS and primary SS suggests an independent onset of GBS and the co-existence of these autoimmune diseases in patients with multiple autoantibodies. Majority of patients with GBS and primary SS experience benign disease course.

Absence of Anti-Babesia microti antibody in commercial intravenous immunoglobulin (IVIG).

BACKGROUND: Babesiosis is a worldwide emerging protozoan infection that is associated with a spectrum of disease severity from asymptomatic infection to severe organ damage and death. While effective treatment strategies are available, some immunocompromised patients experience severe acute and prolonged/relapsing illness due in part to an impaired host antibody response. Intravenous immunoglobulin (IVIG) has been used as an adjunctive therapy in some immunocompromised babesiosis patients, but its therapeutic effect is uncertain. We evaluated the presence of Babesia microti antibodies in commercial samples of IVIG. METHODS/PRINCIPLE FINDINGS: The presence of B. microti antibodies in commercial samples of IVIG were tested using an immunofluorescence assay. A subset of samples was then tested for B. microti antibodies using an enzyme linked immunosorbent assay. Out of 57 commercial IVIG samples tested using IFA, and 52 samples tested using ELISA, none were positive for B. microti antibodies. CONCLUSIONS: Commercially available IVIG may not be of therapeutic benefit for babesiosis patients. Additional sampling of IVIG for B. microti antibody and a clinical trial of babesiosis patients given IVIG compared with controls would provide further insight into the use of IVIG for the treatment of babesiosis.

Determination of procoagulant activity in human normal immunoglobulin preparations for therapeutic use by FXIa chromogenic assay: Evaluation of test kit sensitivity, reference standard performance and product formulation effects on the FXIa assay.

In 2010, the reporting of thrombotic adverse events for one subcutaneous and certain intravenous immunoglobulins (IGs) raised some concerns. In Europe, regulatory bodies rapidly revised compendial specifications for therapeutic IGs to ensure they do not exhibit thrombogenic (procoagulant) activity (PCA). At the global level, a working group (GWG) was launched with the aim of assessing PCA measurement methods and limits, considering results obtained by human IG manufacturers during in-process controls. The GWG created three dedicated subgroups to investigate the FXIa chromogenic assay, the non-activated partial thromboplastin time (NAPTT) test and the thrombin generation assay (TGA). The European Directorate for the Quality of Medicines & HealthCare (EDQM) was responsible for co-ordinating the subgroup in charge of evaluating the FXIa chromogenic assay in a study that assessed the sensitivity and robustness of two commercial chromogenic FXIa test kits. The impact of IG product formulation on FXIa recovery and the suitability of PCA-containing IG products as potential reference standards/controls were also assessed. IG materials representative of marketed products were provided to four laboratories for a study that was carried out in two steps: 1) two chromogenic FXIa test kit manufacturers assessed the performance and determined optimal test conditions by their respective methods, 2) two OMCLs studied both kits using an optimised study design. Regarding sensitivity, the study results identified suitable dose-response intervals and limits with both chromogenic FXIa test kits. This allowed the establishment of dilution ranges for optimal detection of FXIa/PCA in 5 % and 10 % IG products in the range of 1-6 mIU/mL. However, careful optimisation of the sample dilutions was required (notably to avoid potential matrix effects) and the choice of the mode of data acquisition (kinetic or end-point method) contributed to sensitivity in routine use. Importantly, the composition of IG products was of minor concern for FXIa determination with both test kits. Potential reference materials evaluated in the study behaved as expected and could be useful should a separate reference standard to the FXIa WHO IS be deemed necessary in future.

Combination of S100A12/TLR2 signaling molecules and clinical indicators in a new predictive model for IVIG-resistant Kawasaki disease.

Although intravenous immunoglobulin (IVIG)-resistant Kawasaki disease (KD) presents with persistent inflammatory stimulation of the blood vessels and an increased risk of coronary artery dilatation. However, the pathogenesis of this disease is unclear, with no established biomarkers to predict its occurrence. This study intends to explore the utility of S100A12/TLR2-related signaling molecules and clinical indicators in the predictive modeling of IVIG-resistant KD. The subjects were classified according to IVIG treatment response: 206 patients in an IVIG-sensitive KD group and 49 in an IVIG-resistant KD group. Real-time PCR was used to measure the expression of S100A12, TLR2, MYD88, and NF-κB in peripheral blood mononuclear cells of patients, while collecting demographic characteristics, clinical manifestations, and laboratory test results of KD children. Multi-factor binary logistic regression analysis identified procalcitonin (PCT) level (≥ 0.845 ng/mL), Na level (≤ 136.55 mmol/L), and the relative expression level of S100A12 (≥ 10.224) as independent risk factors for IVIG-resistant KD and developed a new scoring model with good predictive ability to predict the occurrence of IVIG-resistant KD.

A rare clinical presentation of COVID 19: opsoclonus-myoclonus ataxia syndrome.

INTRODUCTION: Coronavirus disease 2019 (COVID-19) can have symptoms like many neurological diseases, and one of the rare forms of these presentations is opsoclonus-myoclonus ataxia syndrome (OMAS). The pathogenesis of OMAS in adults has not been clearly elucidated and OMAS can be fatal. CASE PRESENTATION: We present a 71-year-old male patient who was admitted to the emergency department with complaints of involuntary tremor-like movements in his hands, feet and mouth, and speech impediment for three days, and was followed up with COVID-19. The patient was diagnosed with OMAS and clonazepam treatment was started. He died three days later due to respiratory arrest. Our case is the first case diagnosed with COVID-19-associated OMAS in Turkey. DISCUSSION: OMAS has no definitive treatment. Early diagnosis and initiation of corticosteroids and intravenous immunoglobulin (IVIG) therapy, if necessary, can be life-saving. In COVID-19 patients with unexplained clinical findings, awareness of different and rare diseases and a multidisciplinary approach has vital importance.

Gestational alloimmune liver disease with alpha thalassaemia in a neonate.

A term baby presented with cholestatic jaundice since birth. She was diagnosed as gestational alloimmune liver disease-neonatal haemochromatosis (GALD-NH) on evaluation. The baby received intravenous immunoglobulin (IVIG) and recovered gradually from the illness. She was also diagnosed with alpha thalassaemia during the course of evaluation, confirmed by genetic testing. NH is a very rare disorder that results in fetal loss or neonatal death due to liver failure. NH is now known to be a phenotypic expression of GALD. Worldwide, NH is seen in less than one in a million pregnancies. The mortality rate of GALD has traditionally been around 80% with almost all babies needing liver transplantation, with advent of maternal and neonatal IVIG treatment, this has reduced significantly. There is no reported case of GALD-NH treated successfully with IVIG from India. Here, we report an interesting case of GALD-NH with alpha thalassaemia.

A Bayesian Network Meta-Analysis of the Effect of Targeted Therapies on the Total Length of Hospital Stay in Children with Drug-Induced Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis Syndrome.

Background: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare potentially life-threatening hypersensitivity disorders characterized by widespread skin and mucosal involvement. However, there is no standardized evidence-based treatment to reduce the complications of SJS/TEN. This article aims to compare the efficacy of different treatments for pediatric SJS/TEN in terms of length of hospital stay (LOS) using a Bayesian network meta-analysis (NMA). A Bayesian NMA is used to compare and combine evidence from multiple studies and allows clinicians to estimate the relative effectiveness of different treatments/interventions while accounting for heterogeneity in the available evidence. Methods: We conducted a comprehensive electronic database search for studies compatible with our inclusion criteria. Six studies with 103 patients were included in the NMA; of them, 37 patients were treated with intravenous immunoglobulin (IVIG), 37 with systemic corticosteroids (CS), 23 with IVIG + CS, and 3 with Etanercept (ET) + CS. Patients with a median age of 10 years were included in the study. Results: CS had the highest probability of being the most optimal treatment for SJS/TEN in terms of shorter LOS based on the Surface Under the Cumulative Ranking curve levels, and CS + IVIG was associated with a statistically nonsignificant trend toward shorter LOS than IVIG alone. Remarkably, none of the treatments showed a significant benefit over the other interventions in terms of LOS. Conclusion: Current evidence suggests that coadministration of CS and IVIG may be associated with a shorter LOS than IVIG alone. Further research with larger randomized controlled trials is needed to reach a definitive conclusion about the efficacy of specific therapy on LOS in pediatric SJS/TEN and to establish more definitive treatment guidelines.

Intravenous immunoglobulin protects the integrity of the intestinal epithelial barrier and inhibits ferroptosis induced by radiation exposure by activating the mTOR pathway.

Radiation exposure often leads to serious health problems in humans. The intestinal epithelium is sensitive to radiation damage, and radiation causes destruction of the intestinal epithelial barrier, which leads to radiation enteritis (RE), the loss of fluids, and the translocation of intestinal bacteria and toxins; radiation can even threaten survival. In this study, we aimed to explore the influence of IVIg on the integrity of the intestinal epithelial barrier after RE. Using a RE mouse model, we investigated the protective effects of intravenous immunoglobulin (IVIg) on the epithelial junctions of RE mice and validated these findings with intestinal organoids cultured in vitro. In addition, transmission electron microscopy (TEM), western blotting (WB) and immunostaining were used to further investigate changes in intestinal epithelial ferroptosis and related signaling pathways. When RE occurs, the intestinal epithelial barrier is severely damaged. IVIg treatment significantly ameliorated this damage to epithelial tight junctions both in vivo and in vitro. Notably, IVIg alleviated RE by inhibiting intestinal epithelial ferroptosis in RE mice. Mechanistically, IVIg promoted activation of the mTOR pathway and inhibited ferroptosis in the intestinal epithelium of mice. Rapamycin, which is a potent inhibitor of the mTOR protein, significantly abolished the protective effect of IVIg against radiation-induced damage to intestinal epithelial tight junctions. Overall, IVIg can prevent RE-induced damage to the intestinal epithelial barrier and inhibit ferroptosis by activating the mTOR pathway; this study provides a new treatment strategy for patients with RE caused by radiotherapy or accidental nuclear exposure.

Case report: Successful treatment of an anti-D2R and DPPX antibody-associated autoimmune encephalitis patient with high-dose methylprednisolone and intravenous immunoglobulin.

Background: Autoimmune encephalitis is a neurological condition caused by abnormal immune responses, manifesting as cognitive impairments, behavioral abnormalities, and seizures. Its diagnosis depends on the detecting neuronal surface antibodies in serum or cerebrospinal fluid. Despite recent advances in understanding, clinical recognition remains challenging, especially with rare antibodies such as anti-dopamine D2 receptor (D2R) and anti-dipeptidyl-peptidase-like protein 6 (DPPX) antibodies. Delayed diagnosis can lead to severe complications. This case presentation emphasizes the diagnostic intricacies and effective treatment of the anti-D2R and DPPX antibody-associated autoimmune encephalitis. Case description: The patient presented with a 3-day history of fatigue and limb soreness followed by a 3-h episode of confusion and limb convulsions. Upon admission to our facility, the initial diagnosis included status epilepticus, aspiration pneumonia, metabolic acidosis, respiratory alkalosis, and suspected encephalitis. Despite receiving antiepileptic, anti-infection, and antivirus therapy, the patient's condition deteriorated. Both computed tomography (CT) scan and magnetic resonance imaging (MRI) of the brain showed no significant abnormalities. No pathogen was identified in the cerebrospinal fluid (CSF). However, further CSF and serum examination revealed positive results of anti-D2R and anti-DPPX antibodies, confirming a diagnosis of anti-D2R and DPPX antibody-associated autoimmune encephalitis. The patient underwent a comprehensive treatment regimen, including high-dose methylprednisolone pulse therapy combined with intravenous immunoglobulin (IVIG), antiviral and anti-infection treatments, and antiepileptic medications. Significant clinical improvement was observed, and by the 18th day of admission, the patient was stable and coherent. Conclusions: The current patient represents the first reported case of double-positive autoimmune encephalitis for anti-D2R and DPPX antibodies, with epilepsy as a prominent feature. High-dose methylprednisolone pulse therapy combined with IVIG has shown significant safety and efficacy in treating anti-D2R and DPPX antibody-positive autoimmune encephalitis-associated epilepsy.