Immunoglobulin Infusion Research Articles

A Study of Tolerability, Satisfaction, and Cost Reduction Using a 10% Immunoglobulin Product at Higher Administration Rates.

Gammaplex 10% (immune globulin intravenous [human], Bio Products Laboratory, Ltd) can be administered with a 15-minute rate-escalation protocol. This analysis examined safety, patient satisfaction, and cost savings in 49 patients administered Gammaplex 10% via rapid infusion over 11 months. Fourteen patients reported 38 adverse reactions, 37 of which were deemed minor/moderate. Patient satisfaction was very good/outstanding. Infusions were estimated to be 2.4 hours shorter than previously administered intravenous immunoglobulin infusions, saving $151.61 per visit in nursing costs. Rapid infusion of Gammaplex 10% was found to be a safe option to reduce the costs of intravenous immunoglobulin treatment while maintaining patient satisfaction.

M225 SUCCESSFUL TREATMENT OF IVIG RELATED ASEPTIC MENINGITIS WITH COLCHICINE, REPORT OF 3 PATIENTS

Intravenous Immunoglobulin infusions are effective therapy for a multitude of conditions, both deficiency of immune function as well as auto-inflammatory disease. A major obstacle to successful treatment with this therapy has been the development of severe headaches, considered aseptic meningitis, beginning during therapy or within a few days after the treatment. We report the first recognized cases of treatment of this severe side effect with colchicine, for both High dose and replacement protocols.

2658. Meningitis in Kidney Transplant Recipients: TransMéninges, a French Multicentric Retrospective Cohort Study

BackgroundThe management of meningitis requires the prompt introduction of high-dose probabilistic anti-infectious therapy. The literature reporting on meningitis in kidney transplant recipients (KTR) is scarce and no recommendation exists for this specific population.MethodsWe retrospectively included all adult KTRs diagnosed with meningitis (cerebro-spinal fluid (CSF) cell count >10/mm3 or positive fungal antigen or direct examination) between 2007 and 2018 in 16 French hospitals. Clinical, biological, and therapeutic data, and 1-year kidney and patient survival were collected.ResultsMeningitis occurred in 134 KTRs (mean age 57+/11.8 years, 56% male), after a median time of 27 months (IQR 8–65); 25% of patients received an immunosuppressive treatment before kidney transplantation, induction treatment included lymphocyte-depleting antibodies in 63%, and 53% presented diabetes (34% before and 19% after the transplantation). The etiologies included Cryptococcus neoformans (30%), Herpesviridae (22%, including Varicella-Zoster Virus 15%), idiopathic forms (11%), Gram-negative bacilli (8% of which 20% produced an extended spectrum β-lactamase), %), infusion of intravenous immunoglobulins (6%), post-transplant lymphoproliferative disorders (5%), Aspergillus fumigatus (4%), Listeria monocytogenes (4%), Enterovirus (4%), and Mycobacterium tuberculosis (3%).The most common symptoms were fever (82.5%), headaches (75%), encephalitis (55%), and convulsion (22.5%). CSF hypercellularity (found in 92% of the cases) was lymphocytic in 65% of the cases and neutrophilic in 35%. Initial anti-infectious therapy was inappropriate in 27% of the cases. One-year patient, graft, and death-censored graft survival rates were 84%, 76%, and 89%, respectively.ConclusionMeningitis after kidney transplantation encompasses a wide range of causes, with C. neoformans and VZV explaining more than 50% of the cases. Gram-negative bacilli are the most represented bacteria with a high rate of antimicrobial resistance. Treatment guidelines should be reconsidered in the specific population of KTRs as the etiology greatly differs from what is observed in the general population.Disclosures All authors: No reported disclosures.

2. Two cases of anti-MDA5 positive dermatomyositis with rapidly progressive interstitial lung disease

2. Two cases of anti-MDA5 positive dermatomyositis with rapidly progressive interstitial lung disease

Assessment and prevention of cytomegalovirus infection in allogeneic hematopoietic stem cell transplant and in solid organ transplant: A multidisciplinary consensus conference by the Italian GITMO, SITO, and AMCLI societies.

Cytomegalovirus (CMV) remains a major cause of morbidity and mortality in allogeneic hematopoietic stem cell transplantation (allo-HSCT) and solid organ transplantation (SOT) recipients. In view of the uncertainties on the assessment and prevention of CMV infection in both transplant procedures, three Italian scientific societies for HSCT and SOT and for Clinical Microbiology appointed a panel of experts to compose a framework of recommendations. Recommendations were derived from a comprehensive analysis of the scientific literature and from a multidisciplinary consensus conference process. The lack of adequate clinical trials focused on certain diagnostic procedures, and antiviral intervention forced the panel to use the methods of consensus for shaping some recommendations. Recommendations concerning the two types of transplant were given for the following issues: assessment of pretransplant CMV serostatus, immunological monitoring after transplant, CMV prophylaxis with antivirals, CMV preemptive strategy, and CMV prophylaxis with immunoglobulin infusion and with adoptive immunotherapy. The questions raised by and the recommendations resulting from this consensus conference project may contribute to the improvement of certain crucial aspects of the management of CMV infections in allo-HSCT and in SOT populations.

Safety of an Abbreviated Transition Period When Switching From Intravenous Immunoglobulin to Eculizumab in Patients with Treatment-Refractory Myasthenia Gravis: A Case Series.

Case seriesPatient: —Final Diagnosis: Generalized myasthenia gravisSymptoms: Muscle weaknessMedication: IVIg • eculizumabClinical Procedure: Transition from IVIg to eculizumabSpecialty: NeurologyObjective:Unusual setting of medical careBackground:Eculizumab is a terminal complement inhibitor used to treat myasthenia gravis in patients refractory (because of insufficient efficacy or intolerance) to other therapies, including intravenous immunoglobulin. However, information is lacking on how to transition patients from intravenous immunoglobulin to eculizumab, while avoiding a crossover effect of intravenous immunoglobulin and minimizing the risk of a transient worsening of symptoms if treatment that may be at least partially effective is interrupted. The aim of this study was to determine whether eculizumab can be safely initiated before complete intravenous immunoglobulin washout, using a standardized protocol.Case Report:A series of 13 patients with generalized treatment-refractory myasthenia gravis were transitioned to eculizumab 10–14 days after their last intravenous immunoglobulin infusion. Patients’ clinical status was assessed before and 6 weeks after transition using the Myasthenia Gravis Composite Score. Most patients (8/13; 62%) had received ≥3 immunosuppressants as well as intravenous immunoglobulin. The median (range) Myasthenia Gravis Composite Score before and 6 weeks after transition was 21 (11–29) and 12 (6–18), respectively. Clinically significant improvements (score decrease ≥3) were observed in all patients. Two patients experienced mild myalgia during transition.Conclusions:In this case series, patients with treatment-refractory myasthenia gravis were successfully transitioned to eculizumab 10–14 days after their last intravenous immunoglobulin infusion without any significant safety concerns.

P096 Successful vedolizumab therapy in an elderly patient with ulcerative colitis and refractory immune thrombocytopenic purpura

BACKGROUND: Extraintestinal manifestations (EIM) are common in inflammatory bowel disease (IBD) patients and may occur before or after the diagnosis of IBD. In general, the most common EIM usually affect joints, skin and eyes. However, less often other systems can also be affected. The occurrence of immune thrombocytopenic purpura in IBD patients is rare and poorly described in the literature. CASE: A 61-year-old man was admitted with a history of diarrhea. Admission laboratory tests showed anemia and iron deficiency. There were also mild thrombocytopenia. The patient reported a history of ulcerative colitis (UC) diagnosed 7 years ago (pancolitis). There were several clinical recurrences, with episodes of severe anemia, requiring hemotransfusion in some occasions. He used 5-ASA without improvement. He reported different courses of prednisone 40 mg per day, with clinical remission. He used azathioprine for about 6 months, but there was no clinical remission free of corticosteroids. Colonoscopy showed a suggestive aspect of UC (pancolitis), with severe endoscopic activity (Mayo ES 3). The patient underwent corticosteroid therapy. He presented clinical remission and was discharged in order to initiate biological therapy on an outpatient basis. After discharge, the patient suspended steroid therapy on his own and did not return to the office for follow-up. Two months later, he developed a new UC relapse and was hospitalized again. Laboratory tests showed a significant worsening of thrombocytopenia (5,000 per mm3 platelets). Prednisone was performed again. The patient achieved clinical remission but maintained severe thrombocytopenia. The diagnosis of Immune thrombocytopenic purpura (ITP) refractory to corticosteroids was considered. Then, the patient underwent different immunoglobulin infusion sessions. He presented a temporary improvement in platelet count (20,000 to 50,000 per mm3), but in a few weeks he returned to severe thrombocytopenia (< 5,000 per mm3). Patient was then treated with rituximab. After the third dose, he developed septic shock. It improved after meropenem use. Due to the severe infectious episode, rituximab therapy was discontinued and romiplostim treatment was initiated. There was partial improvement of the thrombocytopenia and the patient maintained the weekly use of the medication. In August 2017, the patient started vedolizumab. After 14 weeks he evolved with clinical remission free of corticosteroids. The patient remained in clinical remission without corticosteroids in the first 12 months of treatment with vedolizumab. Colonoscopy performed 11 months after the beginning of the biological therapy showed mucosal healing (Mayo ES 1). He was maintained throughout this period with progressive improvement of the platelet count, with weekly doses of romiplostim. After the eleventh month of treatment with vedolizumab, there was a reduction in the dose of romiplostim due to improved thrombocytopenia (>200,000 per mm3). DISCUSSION: Physicians should be alert to the occurrence of severe thrombocytopenia in a IBD patient. ITP is considered a rare extraintestinal manifestation and appears to be related to the activity of IBD. In the case reported, clinical and endoscopic remission induced by vedolizumab seems to have been a decisive factor for the gradual improvement of thrombocytopenia, including the partial weaning of romiplostim.

Clinical study on varicella zoster virus infection in children following allogeneic hematopoietic stem cell transplantation

Objective To analyze the risk factors of varicella zoster virus(VZV) infection after allogeneic hematopoietic stem cell transplantation(allo-HSCT) in children, and to provide reference for the diagnosis, monitoring and prophylaxis of VZV infection after allo-HSCT. Methods A total of 367 patients, who underwent allo-HSCT in Pediatric Transplantation Center of Nanfang Hospital Affiliated to Southern Medical University from January 2012 to June 2015 were collected.Clinical characteristics and risk factors of the patients complicated with VZV after allo-HSCT were retrospectively analyzed. Results Thirty-four patients (9.26%) were complicated with VZV infection after allo-HSCT.The median onset time was 96.5 d(19-326 d). Two of 34 patients relapsed 3 times, 1 case of them relapsed twice, 3 cases of them relapsed once, and 4 cases of 34 patients were complicated with VZV encephalitis.All cases were treated with antivirus drugs, infusion of immunoglobulin, reduction of immunosuppressant dosages, with external use of Acyclovir ointment.The median therapy time was 13 days (7-28 days). All of their herpes subsided, and neurological symptoms such as headache, vomiting and convulsion disappeared.VZV-DNA both in blood and cerebrospinal fluid turned negative.No patient had herpetic dissemination and visceral involvement, and no one died directly of VZV infection.Results indicated that age(χ2=6.863, P=0.009), underlying disease(χ2=14.793, P=0.022), type of HSCT(χ2=14.459, P=0.001) and resource of stem cell (χ2=20.585, P=0.002) were significant risk factors for VZV infection after allo-HSCT, while sex (χ2=0.106, P=0.745) and antithymocyte globulin in conditioning regimen(χ2=0.010, P=0.921) had no relation to it. Conclusions VZV infection mainly occur within 12 months after allo-HSCT and is prone to be complicated with VZV encephalitis.The effect of Acyclovir is good.Monitoring and prophylaxis of VZV infection after allo-HSCT should be strengthened in children with high risk factors. Key words: Varicella zoster virus; Allogeneic Hematopoietic stem cell transplantation; Child; Prophylaxis

Etanercept as Adjunctive Primary Therapy in Kawasaki Disease.

* Abbreviations: BSA — : body surface area CA — : coronary artery IVIg — : intravenous immunoglobulin KD — : Kawasaki disease TNF — : tumor necrosis factor Primary treatment of patients with Kawasaki disease (KD) with a single infusion of intravenous immunoglobulin (IVIg) reduces the risk of coronary artery (CA) dilatation and aneurysms, but IVIg resistance occurs in 10% to 20% of patients.1 Intensification of primary therapy with adjunct anti-inflammatory therapies to reduce IVIg resistance is therefore of considerable interest, either universally or in selected subgroups. Among the armamentarium of anti-inflammatory agents that could be added to IVIg therapy, blockade of inflammatory cytokines (such as tumor necrosis factor [TNF]), which are markedly increased in KD, is logical. However, a randomized trial of infliximab, a chimeric monoclonal anti-TNF antibody, in unselected patients with KD did not reduce IVIg resistance, defined as recurrent or persistent fever at least 36 hours after completion of the initial IVIg infusion.2 Infliximab was associated with fewer days of fever and more rapid improvement in inflammatory markers but only a borderline smaller dimension of the left anterior descending CA at 2 weeks, which is of uncertain clinical significance.2 In this edition of Pediatrics , Portman et al3 report results of a North American multicenter randomized controlled trial of etanercept, a soluble TNF-receptor fusion protein, as adjunctive primary treatment in unselected patients with … Address correspondence to David P. Burgner, FRACP, PhD, Infection and Immunity Theme, Murdoch Children’s Research Institute, Royal Children’s Hospital, 50 Flemington Rd, Parkville, VIC 3052, Australia. E-mail: david.burgner{at}mcri.edu.au

Usefulness of an Initial Single Intravenous Immunoglobulin Infusion with Delayed Use of Aspirin against Kawasaki Disease Relapse: A Single-Center Retrospective Study

Background: Kawasaki Disease (KD) relapse is a risk factor for Coronary Artery Lesion (CAL) development. However, the frequency and outcomes of patients with relapse remain unclear. Objective: To determine the frequency and outcomes of patients with KD relapse and to ascertain the usefulness of treatment with initial single intravenous immunoglobulin (IVIG) therapy (2g/kg) with delayed use of aspirin (DUA). Materials and Methods: The outcomes of 207 patients who underwent initial single IVIG therapy at 2 g/ kg/ dose with DUA for KD were analyzed retrospectively. The patient data were divided according to whether the patients had relapses (relapse group, n=5) or not (non-relapse group, n=202). KD presentations were considered as relapses when a second episode appeared within 2 months of the first one. Stat Flex version 6 for Windows was used for all statistical analyses. Chi-square, Fisher’s exact, and Mann-Whitney U tests were used as appropriate, with sample size considerations. Results: The frequency of patients with disease relapse was 2.4%. The five patients who experienced relapses (two boys and three girls; median age, 10 months; range, 3 months to 3 years 11 months) received initial IVIG therapy at 5 days of illness. The median day of illness for the relapse was 16 (range, 12-29). No patients with disease relapse developed CAL. The rate of incomplete type, IVIG resistance and CAL, and timing of initial IVIG therapy with regard to the days of illness were similar between the relapse group and the non-relapse group. Three parameters, including serum C-reactive protein, albumin values, and Neutrophil-to-Lymphocyte ratio (NLR) before and after initial IVIG, were similar between the two groups. Although not statistically significant (P=0.055), the median NLR after initial IVIG therapy of the relapse group was higher than that of the non-relapse group (2.48 vs. 0.84). Conclusion: An initial single IVIG therapy (2g/ kg/ dose) with DUA for KD may lead to a low KD relapse frequency and to favorable patient outcomes.

Switching immunoglobulin products, what are the implications? Result of 2018 census of immunology centres

The use of regular infusions of immunoglobulin is well established as a treatment for patients with antibody deficiency and for patients requiring immunomodulation. Although efficacy is believed to be equivalent for the different immunoglobulin products, it is generally regarded as best practice not to switch from one product to another unless there is a clinical reason to change. Changes in commissioning guidance and issues with the supply of some immunoglobulin products to the UK resulted in a requirement for a significant number of patients to switch between immunoglobulin products in 2017-2018. Data from the 2018 UK Primary Immunodeficiency census has been used to evaluate the clinical results of switching. Results from 30 immunology centres reported a total of 802 immunoglobulin product switches. Twelve reactions were recorded, none of which required admission to hospital, one patient was treated with oral corticosteroids, the others required either no treatment or treatment with oral antihistamines. This review of immunoglobulin product switch reactions gives a clearer indication regarding the safety of product switching than has previously been published.

Kawasaki disease triggered by parvovirus infection: an atypical case report of two siblings

BackgroundThere are reports of the familial occurrence of Kawasaki disease but only a few reports described Kawasaki disease in siblings. However, the familial cases were not simultaneous. In these patients the idea of infective agents as trigger must be considered.Case presentationWe describe two siblings with atypical presentations of Kawasaki disease; the sister was first diagnosed as having parvovirus infection with anemia and the brother was diagnosed as having myocarditis.The first patient was a 9-month-old Caucasian girl with fever, conjunctivitis, rash, and pharyngitis, and later she had cervical adenopathy, diarrhea and vomiting, leukocytosis, and anemia, which were explained by positive immunoglobulin M against parvovirus. However, coronary artery lesions with aneurysms were documented at day 26 after fever onset. An infusion of intravenous immunoglobulin and high doses of steroids were not efficacious to resolve the coronary lesions. She was treated with anakinra, despite a laboratory test not showing inflammation, with prompt and progressive improvement of coronary lesions.Her 7-year-old Caucasian brother presented vomiting and fever at the same time as she was unwell, which spontaneously resolved after 4 days. Four days later, he again presented with fever with abdominal pain, associated with tachypnea, stasis at the pulmonary bases, tachycardia, gallop rhythm, hypotension, secondary anuria, and hepatomegaly. An echocardiogram revealed a severe hypokinesia, with a severe reduction of the ejection fraction (20%).He had an increase of immunoglobulin M anti-parvovirus, tested for the index case of his sister, confirming the suspicion of viral myocarditis. He received dopamine, dobutamine, furosemide plus steroids, with a progressive increase of the ejection fraction to 50%. However, evaluating his sister’s history, the brother showed a myocardial dysfunction secondary to Kawasaki shock syndrome.ConclusionsWe report on familial Kawasaki disease in two siblings which had the same infectious trigger (a documented parvovirus infection). The brother was diagnosed as having post-viral myocarditis. However, in view of the two different and simultaneous evolutions, the girl showed Kawasaki disease with late coronary artery lesions and aneurysms, whereas the brother showed Kawasaki shock syndrome with myocardial dysfunction.We stress the effectiveness of anakinra in non-responder Kawasaki disease and the efficacy on coronary aneurysms.

Influenza Immunoglobulin for Adults Hospitalized with Influenza

Background: Despite treatment with licensed antiviral agents, high rates of influenza-related morbidity and mortality occur worldwide. Methods: Adults hospitalized with laboratory-confirmed influenza were randomized (1:1) to a single double-blind infusion of high-titer anti-influenza intravenous immunoglobulin (hIVIG) or saline placebo. The primary endpoint was an ordered categorical outcome, ranging in severity from death to post-discharge resumption of normal activities, assessed at Day 7. The odds ratio (OR) (hIVIG versus placebo) of a favorable outcome was estimated with a proportional odds model. Findings: Of 308 randomized patients, 73% and 27% had influenza A and B, respectively; antiviral use was 95%. As expected, hIVIG produced a robust rise in influenza A hemagglutination inhibition (HAI) titers, and smaller rises in influenza B titers. Viral load declined after 3 days by 1.99 (hIVIG) versus 2.32 log10 copies/mL (placebo) (p=0.49). The OR for favorable outcome was 1.25 (95% confidence interval [CI] 0.79-1.97, p=0.33). ORs for influenza A and B were 0.94 (95% CI: 0.55-1.59) and 3.19 (95% CI: 1.21-8.42), respectively (p=0.02 for difference). This difference between influenza A and B was mirrored for secondary clinical outcomes, changes in viral load, and in sensitivity analyses, overall and by strain. To investigate this outcome further, anti-HA antibody affinities were measured in the hIVIG lots administered, and much stronger antibody affinities for B strains were observed than for A in hIVIG used. Interpretation: Overall, hIVIG was not superior to placebo for adults hospitalized with influenza. In contrast to our pre-study subgroup hypothesis based upon conventional HAI titers in hIVIG, benefit was evident for those with influenza B but not A. Consistent with findings of a contemporaneous anti-influenza plasma trial (IRC005), adjunctive immunotherapy appears ineffective for severe influenza A. The beneficial effect of hIVIG for influenza B is supported by antibody affinity analyses, but confirmation of clinical benefit is warranted. Clinical Trial Registration: ClinicalTrials.gov Identifier: NCT02287467. Funding: NIAID, NIH. Declaration of Interest: There are no competing interests to declare in regard to this manuscript submission. Ethical Approval: The trial was approved by the institutional review board or ethics committee for each clinical site. All patients provided written informed consent.

Cardiac Transplantation across Preformed HLA-Antibody Barriers: Results of a Peritransplant Desensitization Protocol

Purpose A growing number of patients awaiting heart transplantation presents with preformed anti-HLA antibodies. This allosensitization prolongs waiting times and increases morbidity and mortality. In 2017, we designed aprotocol for peritransplant desensitization of heart-transplanted patients showing preformed anti-HLA donor specific antibodies (pfDSA), i.e. a positive virtual crossmatch. The protocol included: an intraoperative single dose of the IL-6 receptor antibody Tocilizumab (10mg/kg) just before releasing the aortic clamp; 5 sessions of plasmapheresis (PE, 1 before transplantation, 1 during transplantation and 3 thereafter); an infusion (2g/kg) of IgA and IgM-enriched human immunoglobulins G (IgGAM) after the last PE; and a single Rituximab dose (375mg/m2) after IgGAM. IgGAM are repeated every 4 weeks (0.5g/kg) for a maximum of 6 months, if DSA are still positive. Aim of this study was to present the preliminary results of this peritransplant desensitization protocol. Methods Records of heart-transplanted patients at our institution between 01/2017 and 10/2018 were reviewed. Patients with pfDSA (positive virtual crossmatch) formed the case group, remaining patients the control group. Median (IQR) follow-up amounted to 9 (5, 16) months. Results During the study period, among the 42 transplanted patients, 9 (21%) patients formed the case group and the remaining 33 (79%) the control group. All 9 case patients showed pfDSA with >50% pre-transplant panel reactive antibodies (PRA). Pretransplant recipient and donor characteristics did not differ between groups. Post-transplant, no case patients showed severe primary graft dysfunction, but 6 (19%) control patients did (p=0.19). At treatment end, pfDSA were cleared in 4 (44%) patients. At 1-year follow-up, survival was 100% vs. 75% in case and control patients (p=0.18); freedom from biopsy-confirmed rejection (Grade >1R) was 89% vs. 92% in case (n=1) and control (n=2) patients (p=0.78); and from steroid-pulsed therapy 89% vs. 82% in case (n=1) and control (n=5) patients (p=0.76), respectively. One case patient showed minimal AMR (pAMR 1+). Conclusion The present study showed that heart transplantation across positive crossmatch barriers can be feasible and safe. The present peritransplant desensitization protocol yielded good survival and rejection-free survival.

Phenotype and Genotype of a Cohort of Chinese Children with Early-Onset Protein-Losing Enteropathy

To examine the phenotypes and perform next-generation sequencing in children with early-onset protein-losing enteropathy. We performed a retrospective review of 27 children with early-onset protein-losing enteropathy. Patients were characterized on clinical, immunologic, and systemic involvements. Targeted gene panel sequencing and whole-exome sequencing were performed in 9 patients. In 27 patients (55.6% male), median age of disease onset was 173days, and 59.3% had onset of disease before 1year of age. Initial gastrointestinal symptoms included diarrhea (74.1%), vomiting (33.3%), and abdominal distention (48.1%). All patients had hypoalbuminemia, with an average serum albumin concentration of 20.2±5.4g/L. Hypogammaglobulinemia was identified in 72% of the patients. Upper endoscopy showed typical presentation of intestinal lymphangiectasia (n=13). Patients frequently received intravenous albumin and immunoglobulin infusions as well as parenteral nutrition. Next-generation sequencing in 9 patients with available DNA showed 1 patient had compound heterozygous CCBE1 mutations and 2 had novel homozygous DGAT1 mutations. Monogenic diseases were identified in 3 of 9 patients who underwent genetic sequencing. Three subjects (11.1%) died, of whom 2 had homozygous DGAT1 mutations. No significant correlation was found between age of symptom onset, serum albumin, serum IgG, lymphocyte count, CD4+ cells, and mortality. Monogenic diseases may be observed in children with early-onset protein-losing enteropathy, and genetic evaluation with next-generation sequencing should be considered.

Fetal and neonatal alloimmune thrombocytopenia: recommendations for evidence-based practice, an international approach.

Fetal and neonatal alloimmune thrombocytopenia (FNAIT) may result in severe bleeding, particularly fetal and neonatal intracranial haemorrhage (ICH). As a result, FNAIT requires prompt identification and treatment; subsequent pregnancies need close surveillance and management. An international panel convened to develop evidence-based recommendations for diagnosis and management of FNAIT. A rigorous approach was used to search, review and develop recommendations from published data for: antenatal management, postnatal management, diagnostic testing and universal screening. To confirm FNAIT, fetal human platelet antigen (HPA) typing, using non-invasive methods if quality-assured, should be performed during pregnancy when the father is unknown, unavailable for testing or heterozygous for the implicated antigen. Women with a previous child with an ICH related to FNAIT should be offered intravenous immunoglobulin (IVIG) infusions during subsequent affected pregnancies as early as 12weeks gestation. Ideally, HPA-selected platelets should be available at delivery for potentially affected infants and used to increase the neonatal platelet count as needed. If HPA-selected platelets are not immediately available, unselected platelets should be transfused. FNAIT studies that optimize antenatal and postnatal management, develop risk stratification algorithms to guide management and standardize laboratory testing to identify high risk pregnancies are needed.

LIG4 syndrome: a report of four cases and literature review

Objective: To analyze clinical, immunological and genetic characteristics of 4 cases of LIG4 syndrome. Methods: We retrospectively analyzed the clinical data of 4 patients from 3 families with LIG4 syndrome who were admitted to Children's Hospital of the Capital Institute of Pediatrics from June 2017 to May 2018, and reviewed related articles, the clinical, immunological and genetic characteristics of LIG4 syndrome were summarized and analyzed. Results: Those 4 cases (P1 to P4), including 2 males and 2 females, had an average age of 1.5 years. All of them presented with special facial features, such as microcephaly, beak-like-nose, and receding forehead. Three of them presented with delayed physical development. P3 suffered from mental retardation and P4 had feeding difficulty. BCG scars were repeatedly ruptured in 3 cases, 4 cases had pneumonia, 1 case had EB virus infection, 2 cases had cytomegalovirus infection, 1 case had fungal infection, and 1 case had chronic diarrhea. Blood routine tests showed decreased neutrophil and lymphocyte counts. Immunoassay showed decreased absolute count of CD4(+)T lymphocyte and B lymphocyte, with normal CD8(+)T cells. P1, P2 presented with decreased immunoglobulin. All of those patients had LIG4 gene complex heterozygous mutations, of whom one had missense mutation had mild clinical phenotype and another three cases had frameshift mutation presented with severe clinical phenotype. One patient underwent hematopoietic stem cell transplantation, and has established normal immune function. He did not have recurrent infection during one year follow-up period. The other 3 patients had preventive anti-infection treatment and received regular human immunoglobulin infusion, but they still had recurrent infection. In literature review, 67 articles were retrieved, totally 37 case were reported, showing special faces and recurrent infection as characteristic presentation of this disease. Conclusions: The typical manifestations of LIG4 syndrome are microcephaly, special facial features and repeated infection. The average age at diagnosis of LIG4 syndrome was more than one year old. If a patient presented with microcephaly, BCG scar infection and leukopenia, LIG4 syndrome should be considered. Immunoglobulin is decreased at different degrees, and CD4(+) and CD19(+) lymphocyte counts always decrease, Naive T and B cells decrease more prominently, and CD8(+)T cells were normal in patients with typical LIG4 syndrome. It is effective to reconstruction of immune system with bone marrow transplantation in LIG4 syndrome patients.

Bilateral Ischemic Optic Neuropathy Following Intravenous Immunoglobulin

Purpose: The purpose of this work is to report an association between intravenous immunoglobulin (IVIG) infusions and the development of bilateral ischemic optic neuropathy. Methods: A case report is described. Results: A 76-year-old male receiving IVIG infusions developed loss of vision in the left eye and was diagnosed with ischemic optic neuropathy. Two months later, he developed another episode of ischemic optic neuropathy in the contralateral eye. The investigation for giant-cell arteritis, vasculopathy, and infiltrative processes was negative. The patient had minimal improvement in visual acuity over several months of follow-up. Conclusions: Bilateral ischemic optic neuropathy was likely caused by IVIG infusion in this case, given the temporal relationship and the negative workup for other risk factors.

A serious thrombotic event in a patient with immune thrombocytopenia requiring intravenous immunoglobulin: a case report

BackgroundImmune thrombocytopenia is an acquired autoimmune disease. Recently, there has been evidence of thrombotic risk in patients with immune thrombocytopenia, but the mechanism is still inconclusive. Intravenous immunoglobulin infusion therapy is considered an efficient treatment; however, it still is associated with adverse events of fever, chills, and hypotension, as well as serious complications such as thrombosis. We report a case a patient with relapsed immune thrombocytopenia who developed ischemic stroke after an intravenous immunoglobulin infusion.Case presentationA 49-year-old Thai woman with relapsed/refractory immune thrombocytopenia came to our hospital with a large hematoma at the right buttock, and her platelet was decreased to 3 × 109/L. She was admitted to our hospital for intravenous immunoglobulin administration. One hour after completion of intravenous immunoglobulin infusion, the patient’s sister complained that the patient was unconscious and could not move both legs and arms. Emergency computed tomography of the brain showed no abnormal findings, such as brain edema, intracranial hemorrhage, or infarction. One day later, repeat computed tomography of the brain displayed extensive acute ischemic changes and loss of gray-white differentiation of bilateral cerebral hemispheres.ConclusionsWe performed an extensive literature review to determine the possible causes of serious thrombotic events in immune thrombocytopenia between the predictive factors of the disease and intravenous immunoglobulin. Although intravenous immunoglobulin is an effective treatment, thrombotic complications can occur. We emphasize that in patients with atherosclerosis risk factors or thrombophilia, the appropriateness of administering an intravenous immunoglobulin infusion should be carefully evaluated.

Adverse events of intravenous immunoglobulin infusions: a three-year retrospective study in China

Adverse events of intravenous immunoglobulin infusions: a three-year retrospective study in China