Human Intravenous Immunoglobulin Research Articles

Acute Aseptic Meningitis Temporally Associated with Intravenous Polyclonal Immunoglobulin Therapy: A Systematic Review.

An acute aseptic meningitis has been occasionally observed on intravenous polyclonal human immunoglobulin therapy. Since case reports cannot be employed to draw inferences about the relationships between immunoglobulin therapy and meningitis, we conducted a systematic review and meta-analysis of the literature. Eligible were cases, case series, and pharmacovigilance studies. We found 71 individually documented cases (36 individuals ≤ 18years of age) of meningitis. Ninety percent of cases presented ≤ 3days after initiating immunoglobulin therapy and recovered within ≤ 7days (with a shorter disease duration in children: ≤ 3days in 29 (94%) cases). In 22 (31%) instances, the authors noted a link between the onset of meningitis and a rapid intravenous infusion of immunoglobulins. Cerebrospinal fluid analysis revealed a predominantly neutrophilic (N = 46, 66%) pleocytosis. Recurrences after re-exposure were observed in eight (N = 11%) patients. Eight case series addressed the prevalence of meningitis in 4089 patients treated with immunoglobulins. A pooled prevalence of 0.6% was noted. Finally, pharmacovigilance data revealed that meningitis temporally associated with intravenous immunoglobulin therapy occurred with at least five different products. In conclusion, intravenous immunoglobulin may cause an acute aseptic meningitis. The clinical features remit rapidly after discontinuing the medication.

Refractory autoimmune hemolytic anemia in a patient with systemic lupus erythematosus and ulcerative colitis: A case report

BACKGROUND Ulcerative colitis (UC) and systemic lupus erythematosus (SLE) are both systemic immunoreactive diseases, and their pathogenesis depends on the interaction between genes and environmental factors. There are no reports of UC with SLE in China, but six cases of SLE with UC have been reported in China. The combination of these two diseases has distinct effects on the pathogenesis of both diseases. CASE SUMMARY A female patient (30 years old) came to our hospital due to dull umbilical pain, diarrhea and mucous bloody stool in August 2018 and was diagnosed with UC. The symptoms were relieved after oral administration of mesalazine (1 g po tid) or folic acid (5 mg po qd), and the patient were fed a control diet. On June 24, 2019, the patient was admitted for treatment due to anemia and tinnitus. During hospitalization, the patient had repeated low-grade fever and a progressively decreased Hb level. Blood tests revealed positive antinuclear antibody test, positive anti-dsDNA antibody, 0.24 g/L C3 (0.9-1.8 g/L), 0.04 g/L C4 (0.1-0.4 g/L), 32.37 g/L immunoglobulin (8-17 g/L), and 31568.1 mg/24 h total 24-h urine protein (0-150 mg/24 h). The patient was diagnosed with SLE involving the joints, kidneys and blood system. Previously reported cases of SLE were retrieved from PubMed to characterize clinicopathological features and identify prognostic factors for SLE. CONCLUSION The patient was discharged in remission after a series of treatments, such as intravenous methylprednisolone sodium succinate, intravenous human immunoglobulin, cyclophosphamide injection, and plasma exchange. After discharge, the patient took oral prednisone acetate tablets, cyclosporine capsules, hydroxychloroquine sulfate tablets and other treatments for symptoms and was followed up regularly for 1 month, after which the patient's condition continued to improve and stabilize.

Acute rejection post lung transplant.

To review what is currently known about the pathogenesis, diagnosis, treatment, and prevention of acute rejection (AR) in lung transplantation. Epigenomic and transcriptomic methods are gaining traction as tools for earlier detection of AR, which still remains primarily a histopathologic diagnosis. Acute rejection is a common cause of early posttransplant lung graft dysfunction and increases the risk of chronic rejection. Detection and diagnosis of AR is primarily based on histopathology, but noninvasive molecular methods are undergoing investigation. Two subtypes of AR exist: acute cellular rejection (ACR) and antibody-mediated rejection (AMR). Both can have varied clinical presentation, ranging from asymptomatic to fulminant ARDS, and can present simultaneously. Diagnosis of ACR requires transbronchial biopsy; AMR requires the additional measuring of circulating donor-specific antibody (DSA) levels. First-line treatment in ACR is increased immunosuppression (pulse-dose or tapered dose glucocorticoids); refractory cases may need antibody-based lymphodepletion therapy. First line treatment in AMR focuses on circulating DSA removal with B and plasma cell depletion; plasmapheresis, intravenous human immunoglobulin (IVIG), bortezomib, and rituximab are often employed.

Clinical characteristics and response to therapeutic plasma exchange in patients diagnosed with Guillain Barré syndrome in a third level clinic in the city of Cali - Colombia during the years 2016-2022.

Introduction: Guillain Barré syndrome (GBS) presents a non-negligible incidence rate in low-income countries. Intravenous human immunoglobulin (IVIG) and therapeutic plasma exchange (TPR) are the first-line treatments. Aim: The aim of this work is to describe the clinical characteristics and the response to RPT in patients with GBS. Materials and methods: Observational, descriptive, cross-sectional study with analytical scope of patients diagnosed with GBS who were managed with RPT, in two service-providing institutions (IPS) in the city of Cali-Colombia, between 2016 and 2022. outcomes: 33 patients with a mean age of 57+/-16 years were included. After a median stay of 10 days in the intensive care unit (ICU), 75.5% decreased at least one grade on the Hughes scale, 12.1% required mechanical ventilation (MV), 27.3% presented some complication, and there were no fatal outcomes. Prolonged stay in the ICU was significantly associated with an unfavorable clinical evolution. Conclusion: The results suggest that RPT management in an institution with highly complex standards, with early diagnosis and early medical intervention, can contribute to an adequate clinical evolution. Prolonged time in the intensive care unit (ICU) is a prognostic factor to consider in the clinical evolution of these patients. Studies with an analytical design and a larger sample are required to support these findings.

Justification of Intensive care management of children with severe COVID19 (а case study)

the unprecedented COVID-19 pandemic that spread across the world and lasted for more than 3 years had significant medical and social consequences. Despite the fact that in the children's population the coronavirus infection has a milder course and a much lower risk of mortality, there are individual cases with pre-existing comorbidities that cause severe acute respiratory distress syndrome. Thus, in most cases, severe COVID-19 developed in children with pre-existing conditions, including: immunodeficiency, diabetes mellitus, bronchial asthma, etc. Therefore, comorbidities disposed children to progress to severe Covid-19 which requires treatments with more aggressive therapeutic tactics and personalised management. The article presents a clinical case of severe acute respiratory distress syndrome caused by the SARS-CoV-2 virus in an early age child. The patient was observed in the Anesthesiology and Intensive Therapy Department of the Chernivtsi Regional Children's Clinical Hospital. Due to acute respiratory infection, the child has been developing signs of respiratory failure. The available instrumental findings confirmed right lung pneumonia, complicated by pneumothorax. Laboratory tests confirmed leukocytosis, thrombocytopenia, hypertransfusion, increased procalcitonin, increased level of C-reactive protein, D-dimer and interleukin-6 as well as circulating immune complexes. The treatment regimen included respiratory protection (oxygen therapy), support of hemodynamics (infusion of glucose-saline solutions), administration of intravenous normal human immunoglobulin, a short course of parenteral glucocorticosteroids, the use of step-by-step combined antibacterial therapy and a direct-acting antiviral drug (remdesivir), and thromboembolism prophylaxis (low-molecular-weight heparin). Following intensive treatment, the child's condition was characterised by a slow positive dynamics, leading to full recovery. This case demonstrates the need for timely detection of life-threatening conditions caused by COVID-19 and requires an aggressive management of child's condition using a complex intensive therapy.

Складність діагностики рефрактерної хвороби Кавасакі під «маскою» гемобластозу: клінічний випадок із досвіду гематолога

Kawasaki disease (KD) is an acute systemic vasculitis that is the most common cause of acquired heart disease in children under 5 years of age with hyperthermia. Diagnosis of KD is a clinical challenge, given the wide range of clinical manifestations and similarities with many viral and bacterial diseases. Purpose - to describe a clinical case of refractory КD in a three-month-old girl with an emphasis on the importance of echocardiography and coronary angiography for the final verification of the disease, urgent initiation of treatment with minimal suspicion of КD. Clinical case. The article reports on a three-month-old patient with a difficult diagnosis of refractory form of КD. The disease debuted with hyperthermia, enterocolitis, obstructive bronchitis, and hepatoliver syndrome. The manifestations of skin exanthema were initially considered as an allergic dermatitis to the use of a cephalosporin antibiotic. Multisystemic inflammatory syndrome associated with SARS-CoV-2 infection was suspected. After the use of immunosuppressive therapy with mega-doses of dexamethasone and intravenous human immunoglobulin 2 g/kg/day for 3 days, clinical improvement was achieved. Subsequently, the haemogram showed an increase in neutrophilic hyperleukocytosis to the appearance of blast cells, hyperthrombocytosis and severe anaemia. A differentiation was made between a leukemic reaction, the debut of myeloproliferative disease, juvenile myelomonocytic leukaemia. Against the background of a rapid decrease in the number of leukocytes, the girl developed hyperthermia, migratory intermittent maculopapular rash, and foots edema. Laboratory findings included thrombocytosis and an increase in acute-phase parameters. Echocardiography revealed left ventricular dilation, a small amount of excess fluid in the pericardium, dilatation of the left coronary artery evenly to the bifurcation. Computed tomography revealed giant coronary artery aneurysms, which gave grounds to diagnose KD. The study was performed in accordance with the principles of the Declaration of Helsinki. Informed consent of the parents of child was obtained for the study. No conflict of interests was declared by the authors.

Interleukin-1 Blockers: A Paradigm Shift in the Treatment of Recurrent Pericarditis.

Recurrent pericarditis is a problematic clinical condition that impairs the quality of life of the affected patients due to the need for repeated hospital admissions, emergency department visits, and complications from medications, especially glucocorticoids. Unfortunately, available treatments for recurrent pericarditis are very limited, including only a handful of medications such as aspirin/NSAIDs, glucocorticoids, colchicine, and immunosuppressants (such as interleukin-1 (IL-1) blockers, azathioprine, and intravenous human immunoglobulins). Until recently, the clinical experience with the latter class of medications was very limited. Nevertheless, in the last decade, experience with IL-1 blockers has consistently grown, and valid clinical data have emerged from randomized clinical trials. Accordingly, IL-1 blockers are a typical paradigm shift in the treatment of refractory recurrent pericarditis with a clearly positive cost/benefit ratio for those unfortunate patients with multiple recurrences. A drawback related to the above-mentioned medications is the absence of universally accepted and established treatment protocols regarding the full dose administration period and the need for a tapering protocol for individual medications. Another concern is the need for long-standing treatments, which should be discussed with the patients. The above-mentioned unmet needs are expected to be addressed in the near future, such as further insights into pathophysiology and an individualized approach to affected patients.

Use of human intravenous immunoglobulin for the treatment of 12 dogs with newly diagnosed malignant disease and presumed secondary immune-mediated thrombocytopenia.

To evaluate the safety and efficacy of human intravenous immunoglobulin in dogs with newly diagnosed malignancy and presumed secondary immune-mediated thrombocytopenia. Twelve client-owned dogs with newly diagnosed malignant disease and presumed secondary immune-mediated thrombocytopenia were prospectively enrolled to receive a single infusion of human intravenous immunoglobulin at a dose of 0.5 to 1 mg/kg intravenous over 8 hours. A complete treatment response was defined as a platelet estimation of ≥40,000 platelets/μL within 24 hours and a partial response within 48 hours from the completion of human intravenous immunoglobulin infusion. No treatment response was defined as a platelet estimation remaining <40,000 platelets/μL over 48 hours from the completion of the human intravenous immunoglobulin infusion. This pilot study had a prospective, open-label, uncontrolled design. Out of the 12 enrolled dogs, seven completed the study. A complete treatment response to human intravenous immunoglobulin was identified in one lymphoma dog and a partial response was noted in another lymphoma dog. The remaining 10 dogs had no response to human intravenous immunoglobulin. No clinically relevant adverse reactions to human intravenous immunoglobulin occurred in any of the 12 initially enrolled dogs during the infusion and over a 3-month follow-up period for the seven surviving dogs. The results of this study suggest that the use of human intravenous immunoglobulin in dogs with newly diagnosed malignant disease and presumed secondary immune-mediated thrombocytopenia appears safe, but not effective for the treatment of thrombocytopenia. Larger multi-centre, prospective, double-blinded, placebo-controlled, outcome-based, malignancy-specific studies are needed to further evaluate these preliminary findings.

Sialylated IVIg promotes clinical improvements in a rabbit dry eye model by regulating inflammatory cytokines

Dry eye disease (DED) is caused by a loss of homeostasis of the tear film, which results in visual disturbance, ocular surface inflammation and damage, and neurosensory abnormalities. Although it is prevalent in 5–50% of the global population, there are limited clinical options for its treatment. This study explored the potential use of human intravenous immunoglobulin (IVIg) and its enriched fractions of sialylation, sialylated IVIg (sIVIg), as a treatment for DED. Fifteen female New Zealand white rabbits were topically instilled with 0.2% benzalkonium chloride (BAC) twice daily for five consecutive days to induce experimental dry eye. Saline, 0.4% IVIg, or 0.04% sIVIg eye drops were instilled twice daily for 20 consecutive days. Clinical evaluations, such as non-invasive tear break-up time (NIBUT) and corneal fluorescein staining (CFS), were conducted. mRNA levels of mucin 4, mucin 16, TNF-α, IL-1β, MMP9, IL-10, TGF-β, and CD209 in rabbit conjunctival tissues were examined using reverse transcription polymerase chain reaction (RT-PCR) or quantitative RT-PCR (qRT-PCR). The relationships between CD209 family members in rabbits and various mammalian species were analyzed using a phylogenetic tree. IVIg or sIVIg treatment resulted in clinical improvements in the rabbit DED model. The inflammatory cytokines, TNF-α and IL-1β, were increased and mucin 4 and mucin 16, cell surface-associated mucins, were decreased in BAC-induced dry eye. Following IVIg or sIVIg treatment, inflammatory cytokines decreased, whereas the anti-inflammatory cytokine, IL-10, increased substantially. Moreover, a 10-fold lower sIVIg treatment dose resulted in prolonged IL-10 production, representing a significantly improved DED compared to IVIg. Furthermore, the expression of rabbit CD209 mRNA in the rabbit conjunctiva and its close relationship with primate homologs suggest that it may interact with IVIg or sIVIg to promote IL-10 expression, as previously described in humans. At a lower dosage, sIVIg showed a more efficient improvement in DED, making it a promising new candidate medication for DED.

Fc-gamma receptor expression and cytokine responses to intravenous human immunoglobulin in whole blood from non-pregnant and pregnant women and newborns.

Intravenous immunoglobulin (IVIG) can suppress the inflammatory response in adults, but its role in pregnant women and newborns is poorly studied. While the adult immune system is considered mature, it is immature in neonates and suppressed in pregnancy. Since the immune response differs in these 3 groups, the use of IVIG could differentially modulate the immune response. We aimed to explore the effect of IVIG on myeloid blood cells from non-pregnant women, pregnant women and newborns. Whole blood from healthy donors was incubated with lipopolysaccharide (LPS) and/or IVIG. After 0 h, 24 h and 48 h of culture, Fc-gamma receptor (CD16, CD32 and CD64) expression, monocyte and neutrophil bacterial phagocytosis, and cytokine and chemokine concentrations were determined in the supernatant. The baseline expression of monocyte CD16 was higher in newborns than in adult women, but the expression of CD32 and CD64 was similar between groups. Furthermore, LPS and IVIG stimulation, together or separately, did not change Fc-gamma receptor expression in monocytes or neutrophils and did not modify their phagocytosis capacity. On the other hand, IVIG did not downregulate the proinflammatory cytokine response induced by LPS in any group. Interestingly, IVIG induced a strong interleukin 8 (IL-8) response in neonates but not in non-pregnant or pregnant women. Our results show that IVIG did not induce changes in Fc-gamma receptor expression, phagocytic ability, or the cytokine response to LPS in blood cells from neonates, non-pregnant or pregnant women. However, IVIG induced a strong IL-8 response in neonates that could improve immunity.

DOENÇA DE KAWASAKI COM SINTOMAS INICIAIS ATÍPICOS: UM RELATO DE CASO

Introduction: Kawasaki disease (KD) is an acute, self-limited, systemic vasculitis of unknown etiology. The diagnosis is essentially clinical and the treatment is based on the use of intravenous human immunoglobulin (IVIG) and acetylsalicylic acid (ASA) in anti-inflammatory dose, being ideally initiated by the tenth day of the onset of symptoms in order to avoid the complications associated with this pathology. Metodology: This is a case report of a 9-year-old child with Kawasaki syndrome with atypical initial presentation. Discussion: Previously healthy child, presenting febrile jaundice hemorrhagic syndrome and influenza syndrome, associated with radiological changes that could be correlated with SARS-COV-2 infection, without initially ruling out the hypothesis of Pediatric Multisystemic Inflammatory Syndrome (SIM-P). After negative serologies and cultures, there was a progressive remission of symptoms, except for the fever. Criteria for KD were met on the 16th day of evolution, when monotherapy with ASA without IVIG was initiated, with resolution of the fever. Conclusion: It is essential to be aware of the possible variations in the clinical presentation of KD and correlate it with the epidemiological and social context of the patient, due to the morbidity related to this vasculitis.

Case Series of Multisystem Inflammatory Syndrome in Neonates (MIS-N) With a Link to Coagulopathy.

Introduction Multisystem inflammatory syndrome in neonates (MIS-N) is an emerging clinical entity observed in neonates born to mothers with exposure to the SARS-CoV-2 virus before or during the antenatal period. Methods We report 18 neonates diagnosed with MIS-N from retrospectively collected data.A total of 18 neonates (13 term and five late-preterm; 10 males) admitted to the neonatal intensive care unit (NICU) of a tertiary care medical institute, between June 2021 to November 2022, were diagnosed with MIS-N. Results The median age of presentation of the 18 neonates was 1.5 days of life. All the neonates were positive for SARS-CoV-2 IgG antibodies and had elevated D-dimer levels. Respiratory system involvement was the most common (12 of 18 neonates: 66.67%). Ten out of 18 neonates (55.55%) had coagulopathy. Seven of the ten neonates with coagulopathy had central nervous system (CNS) involvement as seizures and/or intracerebral infarcts/bleeds. Cardiovascular and gastrointestinal system involvement was observed in nine (50%) and seven (38.89%) neonates, respectively. One out of 18 neonates died due to intraventricular and cerebral hemorrhage. The mortality rate was 5.55% (n=1). Ten of 18 neonates with coagulopathy required fresh frozen plasma along with repeated therapeutic doses of injection vitamin K. Eight neonates (44.44%) required human intravenous immunoglobulin (IVIG), and three neonates (16.67%) required steroids and IVIG for recovery along with supportive care. Conclusion Coagulopathy can be one of the salient features of presentation in MIS-N. In the immediate post-pandemic era, it is essential that MIS-N is considered in the differential diagnosis of neonates presenting with intracerebral bleeds/infarcts. IVIGand steroids might play an important role in the treatment of neonates with MIS-N.

Preemptive intravenous human immunoglobulin G suppresses BK polyomavirus replication and spread of infection in vitro

BK polyomavirus (BKPyV) infection causes various diseases in immunocompromised patients. Cells from human lung and kidney were infected with BKPyV and treated with commercially available intravenous immunoglobulin G (IVIG). Its effects on BKPyV replication and spread of infection were investigated, focusing on administration timing. IVIG treatment 3 h after infection suppressed BKPyV replication assessed by real-time PCR and expression of the VP1 capsid protein and large T-antigen. IVIG effectively reduced the number of BKPyV-infected cells 2 weeks after infection in an antibody titer-dependent manner. Virus release in the culture supernatants was not influenced by IVIG treatment 6–80 h and 3–9 days after infection. Collectively, IVIG did not affect viral release from infected cells but inhibited the spread of infection by neutralizing the released virus and blocking the new infected cell formation, indicating greater efficacy in early localized infection. BKPyV replication resumed in IVIG-treated cultures at 7 days after IVIG removal. Early prophylactic administration of IVIG is expected to reduce the growth and spread of BKPyV infection, resulting in the reduction of infected cell lesions and prevention of BKPyV-associated diseases.

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

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

A comprehensive evaluation of arginine and its derivatives as protein formulation stabilizers

Arginine and its derivatives (such as arginine ethyl ester and acetyl arginine) have varying degrees of protein aggregation suppressor effect across different protein solutions. To understand this performance ambiguity, we evaluated the activity of arginine, acetyl arginine, and arginine ethyl ester for aggregation suppressor effect against human intravenous immunoglobulin G (IgG) solution at pH 4.8. Both arginine and its cationic derivative arginine ethyl ester in their hydrochloride salt forms significantly reduced the colloidal and conformational stability (reduced kd and Tm) of IgG. Consequently, the monomer content was decreased with an increase in subvisible particulates after agitation or thermal stress. Furthermore, compared to arginine, arginine ethyl ester with one more cationic charge and hydrochloride salt form readily precipitated IgG at temperatures higher than 25 °C. On the contrary, acetyl arginine, which mostly exists in a neutral state at pH 4.8, efficiently suppressed the formation of subvisible particles retaining a high amount of monomer owing to its higher colloidal and conformational stability. Concisely, the charged state of additives significantly impacts protein stability. This study demonstrated that contrary to popular belief, arginine and its derivatives may either enhance or suppress protein aggregation depending on their net charge and concentration.

Immune-mediated hemolysis after administration of human intravenous immunoglobulin in a dog: a case report

A 10-year-old spayed female Maltese presented with purpura and hematemesis. Initial laboratory evaluation revealed immune-mediated thrombocytopenia, but evidence of hemolytic anemia was not identified. Three milligrams of human intravenous immunoglobulin (hIVIG) was administered for 3 hours following prednisolone and mycophenolate mofetil. A pale mucous membrane was identified, and the packed cell volume decreased by 3%. Blood film examination revealed significant spherocytosis with auto-agglutination. Blood transfusions and immunosuppression were continued for 4 days, and hIVIG was discontinued. This report describes a case of increased immune-mediated hemolysis after hIVIG administration, possibly due to new-onset immune-mediated hemolytic anemia or enhanced immunogenicity.

Neurological syndromes and potential triggers associated with antibodies to neuronal surface antigens

BackgroundAutoantibodies against surface neuronal antigens have been associated with specific neurological presentations including autoimmune encephalitis (AE), with variable association with neoplasia and infections. MethodsWe described the phenotype and environmental associations of patients with neurological syndromes associated with antibodies against neuronal surface antigens who were referred to a tertiary center in the South of Brazil. All patients were tested for neuronal autoantibodies using cell-based assays. Clinical, radiological, and laboratory findings were retrospectively reviewed. ResultsWe identified 16 patients, 15 had subacute, and one had a progressive disease course. Among patients with subacute onset, 11 (73 %) were N-Methyl-d-Aspartate receptor (NMDAr-IgG)+, 3 (20 %) were Leucine-rich Glioma-Inactivated-1 (LGI1-IgG)+, and 1 (6 %) was positive for Glycine receptor-IgG. The patient with a progressive disease course had antibodies against IgLON5. Most patients had disease onset in spring and summer suggesting environmental factors for the development of AE. Also, we observed a different pattern of brain lesions when NMDAr-IgG encephalitis followed herpes encephalitis and a previously unreported association with Rosai-Dorfman-Destombe disease. All patients with encephalopathy met criteria for possible AE and all proven NMDAr-IgG+ met criteria for NMDAr-IgG encephalitis. However, only one LGI1-IgG+ patient fulfilled clinical criteria for limbic encephalitis. All but one received high-dose intravenous methylprednisolone, 11 also had intravenous human immunoglobulin, and 4 plasma exchange. Furthermore, all patients received second-line immunotherapy. Importantly, most patients improved with immunotherapy, even when initiated later in the disease course. ConclusionWe identified seasonal variability associated with neuronal surface antibodies suggesting environmental triggers. Also, we described the coexistence of NMDAr-IgG encephalitis with histiocytosis. In our series, most patients received second-line immunotherapy. We observed neurologic improvement after treatment even in cases of delayed diagnosis. Increasing the recognition and availability of tests and treatments for these conditions is of paramount importance in low- and middle-income countries.

Guillian-Barré Syndrome Following Vaccination with Covishield Vaccine: An Adverse Event of Special Interest

Several formulations of vaccines against novel coronavirus have been launched. Thereby, increasing the plausibility of having one or more successful vaccines. India put in place the world’s largest Covid-19 vaccination drive in January 2021. However, the side effects of these vaccines are slowly unfolding. Each new vaccine has potential adverse events of special interest (AESI) that warrant a focused evaluation. We report a very rare neurological complication Guillain-Barré syndrome, immediately following the first dose of COVID vaccination in a young female. An apparently healthy 35 years old female presented with acute onset lower backache, weakness of bilateral lower limbs 11 days after receiving the first dose of Covishield vaccine, which rapidly ascended to upper limbs over 5 days with symmetric motor weakness, power 1/5 in bilateral lower limbs, 3/5 in bilateral upper limbs, with absent deep tendon reflexes. Mild sensory involvement was seen. Evolving dysphagia and hoarseness of voice. Bladder/bowel function, respiratory pattern, and hemodynamics were unaffected. A provisional diagnosis of Guillain-Barre Syndrome was made on basis of clinical presentation, neurological examination, and nerve conduction studies suggesting axonal polyneuropathy. Gradual improvement of the muscle power over the next 2 weeks following Human Intravenous immunoglobulin was seen. The risk-benefit analysis for an individual should be considered prior to Covid-19 vaccination, including the implementation of a pre-vaccination screening checklist to ensure vaccine safety for every vaccine recipient. The vaccine continues to be far more beneficial than detrimental for the public at large. Nonetheless, increased awareness amongst healthcare professionals and the public regarding the potential adverse effects of the vaccine is warranted.

New Developments in the Management of Recurrent Pericarditis.

Recurrent pericarditis is a common and troublesome complication that affects 15%-30% of patients with a previous episode of pericarditis. However, the pathogenesis of these recurrences is not well understood, and most cases remain idiopathic. Recent advances in medical therapy, including the use of colchicine and anti-interleukin-1 agents like anakinra and rilonacept, have suggested an autoinflammatory rather than an autoimmune mechanism for recurrences with an inflammatory phenotype. As a result, a more personalized approach to treatment is now recommended. Patients with an inflammatory phenotype (fever and elevated C-reactive protein level) should receive colchicine and anti-interleukin-1 agents as first-line therapy, whereas those without systemic inflammation should receive low to moderate doses of corticosteroids (eg, prednisone 0.2-0.5 mg/kg/d as an initial dose) and consider azathioprine and intravenous human immunoglobulins in the case of corticosteroid failure. Tapering of corticosteroids should be slow after achieving clinical remission. In this article, we review the new developments in the management of recurrent pericarditis.

#5296 CYTOMEGALOVIRUS INFECTION AFTER COVID-19 IN KIDNEY TRANSPLANT RECIPIENTS: A SINGLE CENTER EXPERIENCE

Abstract Background and Aims Kidney transplant recipients (KTR) have adverse COVID-19 outcomes due to the immunosuppressed status and multiple comorbidities. Cytomegalovirus (CMV) is one of the most frequent opportunistic infections after kidney transplantation. However, data concerning its reactivation after COVID-19 is scarce. Herein, we present a single-center cohort of KRT presenting with CMV infection after COVID-19 and its clinical outcomes. Method Single-center cross-sectional study including 22 KTR with CMV viraemia detected by quantitative polymerase chain reaction up to 6 months after COVID-19, between 2020 and 2022. Demographic and clinical data were collected from the electronic records. Results A total of 22 KTR (13 male) were included with a mean age of 55.5±15.5 years and a median Charlson score of 4 (IQR 3-6). Median time after transplantation was 65 months (IQR 12.5-174.5; 3 KTR with &amp;lt;6 months) and only one patient had been submitted to living-donor transplantation. Eight patients received induction therapy with antithymocyte globulin (ATG). At transplantation time, CMV serologic status had been: 50% D+/R+, 13.6% D+/R- and 4.5% D-/R+. CMV infection prior to COVID-19 had been documented in 6 patients. Concerning COVID-19, severe or critical disease had been reported in 8 patients. Specific therapy had been used in 4 patients: 2 with remdesivir/baricitinib, one with remdesivir and one with molnupiravir. Moreover, immunosuppressive therapy had been adjusted in 11 patients, namely by withdrawing the antimetabolite and increasing steroids (7 patients). Median maximum steroid dose (expressed as equivalents of prednisone dose) had been 40 mg (IQR 20-40) and mean cumulative steroid dose had been 416±317 mg. CMV disease was documented in 8 patients (4 with gastrointestinal involvement) and the mean time of diagnosis after COVID-19 was 10±6 weeks. Maintenance immunosuppression included tacrolimus, antimetabolite and steroid in 12 patients; 6 patients had supratherapeutic levels of tacrolimus at CMV infection diagnosis. Median initial viraemia was 770 copies/mL (IQR 288-4106). Valganciclovir was used in 14 patients (one was already taking it as prophylaxis), ganciclovir in 4 patients and CMV enriched human intravenous immunoglobulin was used in one patient. Nine patients required hospitalization and 2 were transferred to an intensive care unit; one of these 2 patients died. Induction therapy with ATG, CMV serologic status at transplantation time, previous CMV infection, COVID-19 severity or supratherapeutic immunosuppressive drug levels were not associated with CMV infection severity or hospitalization. However, higher maximum steroid dose during COVID-19 was associated with CMV disease (p = 0.038), higher viraemia at diagnosis (p = 0.032) and hospitalization (p = 0.018). Conclusion CMV infection is a common and clinically relevant complication in KTR. Altered immunologic status after COVID-19 may predispose to this infection. In addition, immunosuppressive therapy adjustments, namely the increase in steroid dosing may be very relevant to favor reactivation of CMV. Larger studies are warranted, but careful monitoring could help identifying risk patients earlier and prophylaxis may be considered when increased corticosteroids are prescribed.