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Facilitated subcutaneous immunoglobulin (fSCIG) 10% is an immunoglobulin replacement therapy that utilizes recombinant human hyaluronidase (rHuPH20) to enhance immunoglobulin dispersion and absorption, allowing for longer treatment intervals similar to intravenous immunoglobulin (up to once monthly). fSCIG 10% is indicated in the USA for treating adults and children aged ≥ 2 years with primary immunodeficiency diseases (PIDs). This prospective, non-interventional, open-label, multicenter, post-authorization safety study (NCT02593188) was conducted in the USA from November 2015 to October 2021 to assess the long-term safety of fSCIG 10% in routine clinical practice. Patients with PIDs aged ≥ 16 years who were prescribed and/or had started fSCIG 10% treatment were enrolled. In total, 253 patients were enrolled and included (full analysis set). Participants received fSCIG 10% treatment for a median (interquartile range) of 10.0 (3.5-11.8) months, with the majority of infusions administered every 4 weeks (54.4% [1197/2201 infusions]) and at home (62.6% [1395/2230 infusions]). Overall, 98.5% of infusions were administered without rate reduction, interruption, or discontinuation due to adverse events (AEs). Treatment-related, non-serious AEs were experienced by 52 patients (20.6%, 284 events). Two patients (0.8%) each experienced one treatment-related serious AE (aseptic meningitis and deep vein thrombosis). Development of antibodies against rHuPH20 was uncommon; 14/196 patients (7.1%) tested positive for binding antibodies (titer ≥ 1:160) with no neutralizing antibodies detected. There was no relationship between anti-rHuPH20 antibody positivity and the occurrence of treatment-related serious or non-serious AEs. Long-term, repeated self-administration of fSCIG 10% was well tolerated in US clinical practice by patients with PIDs., (© 2024. The Author(s).)

Purpose: Facilitated subcutaneous immunoglobulin (fSCIG; immune globulin infusion 10% [human] with recombinant human hyaluronidase [rHuPH20]) permits high-volume subcutaneous immunoglobulin (SCIG) infusion, shorter infusion times and reduced dosing frequency relative to conventional SCIG. It is initiated by gradually increasing infusion volumes over time (dose ramp-up) to achieve target dose level (TDL). Whether ramp-up strategies have tolerability or safety advantages over direct initiation at full TDL has not been evaluated clinically., Methods: This phase 1 open-label study assessed tolerability and safety of fSCIG 10% with accelerated or no ramp-up compared with conventional ramp-up in healthy adults (NCT04578535). Participants were assigned to one of the three ramp-up arms to achieve TDLs of 0.4 or 1.0 g/kg/infusion. The primary endpoint was the proportion of infusions completed without interruption or infusion rate reduction owing to treatment-emergent adverse events (TEAEs). Safety was assessed as a secondary endpoint., Results: Of 51 participants enrolled, 50 (98.0%) tolerated all fSCIG 10% infusions initiated (n = 174). Infusion rate was reduced in one participant owing to headache in the 0.4 g/kg/infusion conventional ramp-up arm. Study discontinuations were higher in the no ramp-up arm (70%) versus the conventional (0%) and accelerated (22%) arms at the 1.0 g/kg/infusion TDL. Safety outcomes did not substantially differ between treatment arms., Conclusion: The favorable tolerability and safety profiles of fSCIG 10% in healthy participants support initiating treatment with fSCIG 10% with accelerated ramp-up at TDLs up to 1.0 g/kg. Data support no ramp-up at TDLs close to 0.4 g/kg but additional data are needed for higher doses., (© 2024. The Author(s).)

Aim: To assess the long-term safety of hyaluronidase-facilitated subcutaneous immunoglobulin (fSCIG) 10% in European routine clinical practice. Materials & methods: This prospective, noninterventional, open-label, post-authorization safety study (EUPAS5812) sourced data on adverse events, immunogenicity, treatment regimens and product administration for 106 adult patients prescribed fSCIG 10% across 17 sites in six European countries from July 2014 to February 2020. Results: In total, 1171 treatment-emergent adverse events were reported in 94 patients (88.7%); 25.5% of these events were considered related to fSCIG 10%. Positive binding antibody titers developed in three patients; no neutralizing antibodies to recombinant human hyaluronidase were detected. Conclusion: This real-world study of fSCIG 10% is the longest to date and confirms its long-term safety and tolerability in adults with antibody deficiency diseases.

A 30-year-old, previously healthy adult male received equine rabies immunoglobulins (Ig) (ERIG) along with anti-rabies vaccinations as per protocol for postexposure prophylaxis after an unprovoked rabid dog bite of grade three wound over the shin of the left lower limb. On the 8th day, he developed urticarial rashes beginning from the site of the wound, which gradually became a widespread maculopapular rash. Development of the rash was followed by low-grade fever, nonspecific arthralgias and soreness in the throat. A diagnosis of serum sickness-like illness was made based on history, temporal correlation of administration of ERIG and development of symptoms. He responded well to antihistaminic and a short course of injectable steroids. The purpose of this article is to increase awareness regarding the clinical presentation and management of this rare yet potentially curable adverse event if identified timely., (© Journal of the Association of Physicians of India 2023.)

Immunoglobulin replacement therapy is a life-saving treatment in patients with immunodeficiency and effective in the management of autoimmune disorders. Immunoglobulins are administered intravenously or subcutaneously, with the latter route reducing systemic reactions and providing an option for self-infusion, increasing patient convenience, while decreasing patient burden, healthcare utilization, and costs. A major limitation with subcutaneous administrations is the frequency of infusion due to limited volumes administrable into subcutaneous space, necessitating increased drug concentration, absorption, and dispersion. Increasing the concentration of immunoglobulins from 10 to 20% halves the required volume, but leads to higher dynamic viscosity, limiting infusion rate. Recombinant human hyaluronidase increases dispersion and absorption of immunoglobulins allowing administration of ≤ 600 mL per site, but does not change viscosity. Since the viscosity of fluids depends on temperature, we tested the feasibility of in-line warming of immunoglobulin formulations to physiological temperatures. In vitro analysis showed no negative impact of in-line warming to 38 °C on product quality. Subcutaneous infusion studies in pigs confirmed the feasibility of infusion rates of up to 7.5 mL/min with in-line warmed TAK-881, an immunoglobulin 20% facilitated with recombinant human hyaluronidase. In-line pressures were reduced compared with conventional immunoglobulin 20%, and local tolerance was not altered. Reduction of in-line pressures was more pronounced with thinner needle sets, indicating a potential benefit for patients. In summary, an in in-line warming device can circumvent the limitation of high viscosity, while product quality and local tolerance are maintained. The results of the presented studies warrant further testing in a phase 1 clinical study., (© 2023. The Author(s).)

Introduction: Secondary antibody deficiencies (SAD) are often a side effect of specific therapies that target B cells directly or affect the antibody response indirectly. Treatment of immunodeficiency by immunoglobulin replacement therapy (IgRT) is well established in primary antibody deficiencies, although the evidence for its use in SAD is less well established. To fill the gap and provide opinion and advice for daily practice, a group of experts met to discuss current issues and share best practical experience., Areas Covered: A total of 16 questions were considered that covered use of a tailored approach, definition of severe infections, measurement of IgG levels and specific antibodies, indications for IgRT, dosage, monitoring, discontinuation of IgRT, and Covid-19., Expert Opinion: Key points for better management SID should include characterization of the immunological deficiency, determination of the severity and degree of impairment of antibody production, distinguish between primary and secondary deficiency, and design a tailored treatment protocol that should include dose, route, and frequency of Ig replacement. There remains the need to carry out well-designed clinical studies to develop clear guidelines for the use of IgRT in patients with SAD.

Background: Human immunoglobulins are used for treating diverse inflammatory and autoimmune disorders. Eczema is an adverse event reported but poorly described., Objectives: To describe the clinical presentation, severity, outcome, and therapeutic management of immunoglobulin-associated eczema., Methods: This retrospective and descriptive study included a query of the French national pharmacovigilance database, together with a national call for cases among dermatologists., Results: We included 322 patients. Eczema occurred preferentially in men (78.9%) and in patients treated for neurological pathologies (76%). The clinical presentation consisted mainly of dyshidrosis (32.7%) and dry palmoplantar eczema (32.6%); 5% of cases exhibited erythroderma. Sixty-two percent of the eczema flares occurred after the first immunoglobulin course. Eczema was observed with 13 intravenous or subcutaneous immunoglobulin types and recurred in 84% of patients who maintained the same treatment and in 68% who switched the immunoglobulin type. After immunoglobulin discontinuation, 30% of patients still had persistent eczema., Limitations: Retrospective study, with possible missing data or memory bias., Conclusion: Immunoglobulin-associated eczema occurred with all immunoglobulin types, preferentially in patients with neurologic diseases who required prolonged immunoglobulin treatment. Recurrence was frequent, even after switching the immunoglobulin type, which can lead to a challenging therapeutic situation when immunoglobulin maintenance is required., Competing Interests: Conflicts of interest None disclosed., (Copyright © 2022 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Secondary antibody deficiencies (SAD) may require immunoglobulin replacement therapy (IgRT). While the intravenous route (IVIG) is broadly considered effective in SAD, the use of subcutaneous immunoglobulins (SCIG) is mainly adopted from the experience in primary antibody deficiencies (PAD), where SCIG have been shown to perform as effective as IVIG. However, evidence-based data on SCIG administration in SAD patients are still insufficient. Herein we retrospectively evaluated the efficacy and safety profile of SCIG treatment in 131 SAD patients as compared to a group of 102 PAD patients. We found SCIG being equally effective in reducing annual infectious rate both in SAD and PAD patients. However, SAD patients required lower SCIG dosage and lower IgG through level to achieve similar biological effect in terms of infection burden, at the steady state. SAD patients also showed better correlation between SCIG dose and serum IgG achieved value. Furthermore, within SAD, SCIG were found to work irrespective of the underlying disease. Especially in Non-Hodgkin Lymphoma patients, whose indication to IgRT is still not included in all guidelines and for whom evidence-based data are still lacking, SCIG were as effective as in Chronic Lymphocytic Leukemia or Multiple Myeloma patients, and SCIG discontinuation, without evidence of B cell recovery, led to IgG decline and relapsed infections. Finally, treatment tolerance in SAD patients was comparable to the PAD cohort. Globally, our data suggest that SCIG, as already appreciated in PAD, represent a valuable option in SAD patients, independent on the disease leading to antibody deficiency., Competing Interests: The authors have declared that no competing interests exist.

Objective: Most guidelines recommend the use of nonsteroidal anti-inflammatory drugs (NSAIDs), duloxetine, and tramadol for the nonoperative treatment of osteoarthritis (OA), but the use of them is limited by the tolerability and safety concerns. Lutikizumab is a novel anti-IL-1 α / β dual variable domain immunoglobulin that can simultaneously bind and inhibit IL-1 α and IL-1 β to relieve the pain and dysfunction symptoms. We conducted this network meta-analysis to comprehensively compare the clinical efficacy and safety of lutikizumab with other drugs recommended by guidelines., Methods: We conducted a Bayesian network and conventional meta-analyses to compare the efficacy and safety of lutikizumab with other traditional drugs. All eligible randomized clinical trials, in PubMed, CNKI, EMBASE, and Web of Science databases, from January 2000 to January 2020, were included. The Cochrane risk of the bias assessment tool was used for quality assessment. Pain relief, function improvement, and risk of adverse effects (AEs) were compared in this study., Results: 24 articles with 11858 patients were included. Duloxetine (DUL) had the largest effect for pain relief (4.76, 95% CI [2.35 to 7.17]), and selective cox-2 inhibitors (SCI) were the most efficacious treatment for physical function improvement (SMD 3.94, 95% CI [2.48 to 5.40]). Lutikizumab showed no benefit compared with placebo for both pain relief (SMD 1.11, 95% CI [-2.29 to 4.52]) and function improvement (SMD 0.992, 95% CI [-0.433 to 4.25]). Lutikizumab and all other drugs are of favorable tolerance for patients in the treatment of OA compared with placebo., Conclusions: Lutikizumab, the new anti-Interleukin-1 α / β dual variable domain immunoglobulin, showed no improvement in pain or function when compared with placebo. Selective cox-2 inhibitors and duloxetine remain the most effective and safest treatment for OA. More high-quality trials are still needed to reconfirm the findings of this study., Competing Interests: The authors declare that they do not have any competing interests., (Copyright © 2020 Ziqin Cao et al.)

Immunoglobulin replacement therapy is standard of care in treatment of many primary immunodeficiency diseases. The goal of replacement therapy is to reduce infections in individuals with primary immune deficiency and improve their quality of life. Immunoglobulin replacement therapy is most often lifelong, therefore ease of administration is vital for adherence to treatment. Self-infusion via subcutaneous intravenous immunoglobulin (SCIG) allows patient input to design an individualized and optimal treatment plan. Because SCIG regimens are flexible and allow for increased autonomy, patients receiving SCIG report improved quality of life. This article summarizes the dosing, administration, and adverse event management of SCIG infusions., Competing Interests: Disclosure C. Duff: CSL Behring, nurse consultant; Takeda, presenter; Grifols, nurse consultant. M. Ballow: physician advisory board and speaker bureau for CSL Behring, Takeda, and Grifols; consulting medical director for the Immune Deficiency Foundation; Data Safety Monitoring Board, Prometic, Glenmark., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Facilitated subcutaneous immunoglobulin (fSCIG) replacement therapy is the latest method of IgG administration; however, real-life data are limited. We retrospectively analyzed the everyday experience of fSCIG administration, particularly, the method used to switch from intravenous immunoglobulin (IVIG) or subcutaneous immunoglobulin (SCIG) to fSCIG and the dosing modifications required. Of the 39 adult patients with primary immunodeficiency (PID) who received fSCIG, 34 remained on the therapy at the end of the study. The median observation time was 18 (range, 3-24) months. Two patients were IgG-treatment-naïve; 23 had previously received IVIG and 14 had received SCIG. In 25 cases, a non-ramp-up dosing mode was used to switch to fSCIG (including two half-monthly doses given biweekly in 14 cases, and full monthly doses given in 11 cases), a ramp-up mode was used in six cases; other methods were used in eight cases. The median IgG trough level at baseline was 7.9 g/L ( n = 38), 7.9 g/L ( n = 32) at Month 6, 9.0 g/L ( n = 30) at Month 12, 8.6 g/L ( n = 22) at Month 18, and 9.0 g/L ( n = 11) at Month 24. No serious bacterial infections or hospitalizations due to PID complications occurred. At the end of the study, 24 patients (71%) received fSCIG every 4 weeks, six (18%) received fSCIG every 3 weeks, and four (12%) received fSCIG biweekly. In conclusion, our study provides real-life evidence of clinical efficacy of personalized fSCIG treatment when switching from prior immunoglobulin replacement using various switching modes and dosing frequencies., (Copyright © 2020 Wiesik-Szewczyk, Sołdacki, Paczek and Jahnz-Różyk.)

Background: Hepatitis B immunoglobulin (HBIG) therapy is available in intravenous (IV) or intra-muscular (IM) formulations. Recently, a subcutaneous (SC) formulation was introduced. This study evaluated changes in quality of life when liver transplant (LT) recipients were switched from IV or IM HBIG to the SC formulation., Methods: This multicentre, observational study involved adults who had undergone LT at least 1 year prior to study entry. Quality of life was evaluated using the ITaLi-Q questionnaire, assessing the impact of HBIG therapy on daily activities and patient satisfaction, and the SF-36 Health Survey. Patients completed the questionnaires prior to switching from IV or IM HBIG to SC HBIG and 6 months later., Results: Eighty-six patients were enrolled; before the switch, 68.6% were receiving IM HBIG and 31.4% IV HBIG. After 6 months, significant improvements in 7 of the 8 ITaLi-Q domains were found, particularly side effects, need for support to adhere to the therapy and satisfaction with the HBIG therapy. Significant improvements in several SF-36 domains were documented, including physical functioning, physical and emotional role limitations, pain, social functioning, physical and mental summary scores., Conclusions: The SC route of administration reduces side effects and their interference with daily life, ameliorates negative feelings, and increases patient autonomy.

Subcutaneous immunoglobulin (SCIg) is an emerging therapeutic alternative in the management of myasthenia gravis (MG) due to its potential efficacy, safety, cost effectiveness and ease of administration. At present, there are no systematic reviews that summarized the effects of SCIg in patients with MG. The objective of this study is to determine the efficacy and safety of SCIg in the treatment of adult patients with myasthenia gravis. Relevant records were identified from August 2018 to January 2019 systematic search. Five relevant articles with a total of 34 patients with MG were included in this review. Data on functional disability score and adverse events were obtained. Based on the included uncontrolled studies, the functional disability scores of adult MG patients after SCIg administration showed consistent improvement. Headache and local site injection reactions were the most common adverse events reported. The evidence from limited uncontrolled studies gathered in this review showed that SCIg may improve functional disability in patients with MG. Local and mild adverse events were reported with its administration, but no systemic and serious adverse events were noted., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background and Purpose: To optimize subcutaneous therapy with immunoglobulins, large volume infusion of immunoglobulin G facilitated by pretreatment with hyaluronidase (fSCIG) was compared to conventional infusion of multiple small dosages (cSCIG) in 20 patients with multifocal motor neuropathy., Methods: A randomized, non-inferiority and observer-blinded cross-over design was applied with a treatment period of 24 weeks for each therapy., Results: In 18 patients fSCIG was feasible, two patients leaving the study due to side-effects. The primary study variable, isometric strength, was unchanged, being 100.8% [95% confidence interval (CI) 94.8%-107.1%) in fSCIG and 105.9% (95% CI 99.8%-112.0%) in cSCIG. Secondary end-points of disability, functions, impairments and quality of life showed no differences between the two treatments. Mild and short-lasting generalized side-effects were similar in the two groups, whereas the relative frequency of localized side-effects at the injection site was increased after fSCIG [0.63 (95% CI 0.23-1.00) vs. 0.09 (95% CI 0.00-0.22), P = 0.005]. The preference of the patients favoured fSCIG for two out of five visual analogue scale scores as well as the total mean score of all preferences (P = 0.03)., Conclusions: Facilitated SCIG seems effective, feasible and safe. In addition, it is preferred by patients but is accompanied by a higher frequency of short-lasting localized side-effects., (© 2019 EAN.)

Background: Allergies to cats are the most common animal-origin allergy, and affect approximately 1 in 5 adults worldwide. The prevalence of allergy to furry animals has been increasing, and allergy to cats is a major risk factor for the development of asthma and rhinitis. The diagnosis of cat allergy is now well established. The exact significance of component-resolved diagnosis in the diagnosis of cat allergy remains to be fully understood. Allergen avoidance is effective but often has a psychologic impact. Allergen immunotherapy is not well demonstrated. There is a need for innovative approaches to better manage cat allergens. Next-generation care pathways for asthma and rhinitis will define the place of cat allergen avoidance., Methods and Results: This manuscript, based on content presented at the European Academy of Allergy and Clinical Immunology Congress 2019, provides information on the prevalence and impact of cat allergies and the molecular biology of Fel d 1, the major cat allergen., Discussion: The authors present the scientific basis of a novel care pathway that utilizes anti-Fel d 1 IgY antibodies to safely and effectively neutralize Fel d 1 after its production by the cat but before human exposure., Conclusion: Efficacy of a feline diet with an egg product ingredient containing anti-Fel d 1 IgY antibodies was demonstrated in vitro, ex vivo, and in vivo, and further validated by a pilot exposure study involving cat-allergic human participants., (© 2019 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

Since successful cloning of thrombopoietin (TPO) in 1994, significant advances have been made in the development of recombinant TPO receptor agonists. The US Food and Drug Administration (FDA) has approved 2 agents for use in patients with immune thrombocytopenia (ITP): eltrombopag and romiplostim. Romiplostim is a once-weekly subcutaneous injection that has been shown to increase the platelet count, lessen bleeding, and reduce concurrent medication use in adults with ITP. In December 2018, the US FDA approved romiplostim for use in pediatric patients ≥1 year of age with ITP of >6 months' duration and insufficient response to corticosteroids, immunoglobulins, or splenectomy, based on similarly favorable clinical trial data. In addition, romiplostim is well tolerated, making it an attractive option for the treatment of children. Expansion of off-label romiplostim use is being reported in children for ITP <6 months, neonatal thrombocytopenia, hereditary thrombocytopenias, and chemotherapy- and bone marrow transplant-associated thrombocytopenia. We review here the development of romiplostim with a focus on pediatric use., (© 2019 by The American Society of Hematology.)

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., (© Royal College of Physicians 2019. All rights reserved.)

Sudden cardiac death (SCD) is an unexpected death due to cardiac causes that occurs in a short time period (generally within 1 h of symptom onset) in a person with known or unknown cardiac disease. Patients with cardiomyopathies, myocarditis, ischemic heart disease and cardiac channelopathies are at risk of SCD. However, a certain percentage of autopsy-negative cases of SCD in the young (<35 years) remain unexplained even after a post-mortem genetic testing. Autoantibodies against cardiac proteins may be potentially involved in the pathogenesis of different heart diseases and in the occurrence of unexplained SCD. In this review we analyze clinical and animal studies that elucidate the prevalence of these autoantibodies in patients with different cardiac diseases and their pathophysiological relevance. We propose a classification of the autoantibodies associated with heart diseases and focus on their molecular and cellular effects. Anti-beta adrenergic receptor antibodies and anti-muscarinic acetylcholine receptor antibodies affect myocardial electrophysiological properties and were reported to be the independent predictors of SCD in patients with different heart diseases. Autoimmune mechanism is proposed for cardiac-related adverse reactions following human papillomavirus (HPV) vaccination. The pentapeptid sharing between HPV's antigens, adrenergic receptors and muscarinic acetylcholine receptors supports this assumption. The dysregulating effects of the autoantibodies against calcium and potassium ion channels can be the basis for autoimmune phenocopies of genetic cardiac channelopathies, which are also associated with SCD., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Immunoglobulin preparations are medicines derived from blood used as a replacement therapy for immunodeficiencies or as an immunomodulator. While they are generally well-tolerated, side effects, rarely severe, can nevertheless occur when administered intravenously. They are usually related to an excessive perfusion rate. The recent arrival of safer products administered subcutaneously represents progress in the treatment of patients., (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)

The Serious Transfusion Incident Reporting program (STIR) commenced haemovigilance in relation to RhD immunoglobulin (Ig) administration in 2015. During two years of reporting, 21 reports relating to RhD Ig administration were received. Thirty-three percent (7/21) were related to omission of RhD Ig, putting women at risk of RhD alloimmunisation and adverse consequences in future pregnancies. A recent case reported to STIR highlights poor communication and misinterpretation of pathology results leading to significant morbidity from haemolysis in the fetus. STIR makes recommendations related to education of staff and communication between clinical and laboratory staff to improve the safety of patient care., (© 2018 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists.)

Background: Tenofovir disoproxil fumarate (TDF) administration in the third trimester for pregnant women with high HBV DNA load has been accepted as a wise practice to prevent mother-to-infant transmission (MTIT). However, for those women who missed the optimal time window of antiviral prophylaxis, this treatment is lacking in the current clinical guidelines., Methods: Forty-eight pregnant women who did not receive antiviral prophylaxis before 28 weeks of gestation were screened and were administrated with TDF plus hepatitis B immunoglobulin (HBIG; TDF+HBIG group) or TDF alone (TDF group). HBV DNA inhibition and the safety profile were compared between two groups., Results: A decline of HBV DNA load was observed in both groups after a short period of treatment, and no infant had MTIT. However, compared with the TDF group, the speed of HBV DNA load decline was more rapid (P=0.002) and a much more striking HBV DNA load decline in the first 4 weeks of treatment was exhibited in the TDF+HBIG group (P=0.001). The percentages of mothers with HBV DNA <4 log 10 IU/ml and 3 log 10 IU/ml at delivery were both much higher in the TDF+HBIG group than the TDF group (P=0.034 and 0.024, respectively). TDF and HBIG were found to be well-tolerated with no safety concerns in the mothers and their infants., Conclusions: TDF plus HBIG treatment resulted in a rapid HBV DNA load decline in high-risk women who missed the optimal time window of antiviral prophylaxis in pregnancy, which potentially protected infants from HBV infection.

Objective: There is no consensus on the use of cytomegalovirus (CMV)-specific hyperimmunoglobulins (CSHIGs) for suspected congenital CMV infections during pregnancy, but this therapy is currently used in some countries. The objectives of this study were to describe tolerability and pregnancy outcome following treatment with monthly intravenous CSHIG and compare rates of positive PCR and postnatal symptoms according to whether CSHIGs were given or not., Methods: This retrospective cohort study included all pregnant women who were diagnosed with primary CMV infection or congenital CMV infection at the Centre Hospitalier Universitaire Sainte-Justine (Montreal, QC) between 2005 and 2016. CSHIG was discussed with pregnant women who received positive CMV PCR results from amniotic fluid or if ultrasound anomalies suggested congenital infection and there was serologic evidence of maternal primary infection (therapeutic group). CSHIG was also offered as prophylaxis in pregnant women without fetal ultrasound anomalies but with evidence of maternal primary infection, when amniocentesis either had negative results or was not performed (prophylactic group). A matched analysis was performed to control for timing of maternal infection, amniocentesis, and type and timing of ultrasound anomaly., Results: Sixteen women received CSHIG, and 55 had no CMV-specific treatment. CSHIG treatment was well-tolerated. In bivariate analyses, the risk of congenital CMV infection and postnatal symptoms did not significantly decrease with CSHIG treatment, in both the therapeutic and the prophylactic groups. After matching, there was still no difference in outcomes between CSHIG-treated and untreated women., Conclusion: The effectiveness of CSHIG in preventing congenital CMV infection and its clinical manifestations could not be demonstrated., (Copyright © 2018 Society of Obstetricians and Gynaecologists of Canada. Published by Elsevier Inc. All rights reserved.)

Background & Aims: The combination of hepatitis B immunoglobulin and a nucleos(t)ide analogues has markedly reduced the rate of hepatitis B virus recurrence after liver transplantation; however, the optimal duration of hepatitis B immunoglobulin has not been clarified. This lack of consensus perpetuates the use of different strategies. The aim of this study was to evaluate the risk factors associated to hepatitis B virus recurrence after liver transplantation in a large cohort of patients under different hepatitis B immunoglobulin regimens., Methods: Retrospective multicentre analysis of hepatitis B virus-related liver transplantation recipients receiving combined prophylaxis (hepatitis B immunoglobulin + nucleos(t)ide analogues). The strategy of short-term hepatitis B immunoglobulin was compared to lifelong administration. Hepatitis B virus recurrence was defined as positive HBsAg after liver transplantation., Results: Three hundred and thirty-eight patients were analysed. After a median follow-up period of 72 months, 37 patients (11%) developed hepatitis B virus recurrence. Hepatocellular carcinoma recurrence and lamivudine resistance after liver transplantation were the only factors independently associated to hepatitis B virus recurrence (HR 5.4 [2.3-12] and 9.3 [4.2-20] respectively P < .001). HBsAg reappearance after hepatitis B virus recurrence was transient (16 patients), persistent (15) or alternant (6). The hepatitis B immunoglobulin regimen did not have an impact on the rate or evolution of hepatitis B virus recurrence. Overall, patient survival was good and not influenced by hepatitis B virus recurrence (82% at 5 years). Fulminant liver failure, hepatitis C coinfection or hepatocellular carcinoma at liver transplantation were independent risk factors for lower survival., Conclusions: Liver transplantation is an effective treatment for hepatitis B virus-related liver disease. Since the introduction of combined prophylaxis the rate of hepatitis B virus recurrence is very low. However, lifelong hepatitis B immunoglobulin administration does not seem necessary to reduce hepatitis B virus recurrence., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Tetanus remains a significant burden in many low- and middle-income countries. The tetanus toxin acts within the central nervous system and intrathecal antitoxin administration may be beneficial, but there are safety concerns, especially in resource-limited settings. We performed a pilot study to assess the safety and feasibility of intrathecal human tetanus immunoglobulin in five adults with tetanus before the conduct of a large randomized controlled trial. Intrathecal injection via lumbar puncture was given to all patients within a median 140 (range 100-165) minutes of intensive care unit (ICU) admission. There were no serious adverse effects associated with the procedure although three patients had probably related minor adverse events which resolved spontaneously. Median ICU length of stay was 14 (range 5-17) days. Two patients required mechanical ventilation and one developed a deep vein thrombosis. Within 240 days of hospital discharge, no patients died and all patients returned to work.

Multiple myeloma is commonly associated with a reduction of non-paraprotein immunoglobulins, resulting in a higher risk of infections that represent the leading cause of the patients' death. Therefore, immunoglobulin replacement therapy appears a logical approach. A total number of 46 myeloma patients were randomly enrolled: 24 of them were assigned to receive subcutaneous immunoglobulins, and 22 were controls. The primary endpoint was the evaluation of the annual rate of severe infections in immunoglobulins-receiving patients as compared with those untreated. Subcutaneous immunoglobulins-treated patients showed a significantly lower number of severe infections per year. Adverse events were limited to the site of infusion and were easily manageable. Health-related quality of life was significantly better in subcutaneous immunoglobulins-receiving patients. By decreasing the rate of infections, the prophylactic administration of SCIg improves both adherence to chemotherapy and health-related quality of life, and is cost-effective by reducing the need of hospitalization and the use of antibiotics., (Copyright © 2017. Published by Elsevier Inc.)

Objectives: This analysis assessed the safety of intravenous immunoglobulin (IVIg) in the treatment of patients with neuroimmunological and immunological disorders in a home-based setting., Methods: Adverse reactions (ARs) were assessed in a retrospective review of 1176 patients receiving 28,677 home-based IVIg infusions between 1996 and 2013., Results: Of 1176 patients, 648 (55.1%) experienced IVIg-related ARs; 536 (45.6%) were mild, 78 (6.6%) moderate, and 34 (2.9%) severe. Thirty-seven (3.1%) patients were hospitalized because of ARs; of these, headache was most common (51.4%). Mean number of ARs per patient increased from 1.4 (low dose) to 3.6 (high dose). Incidence of ARs increased from 41% in the first 5-year moving average in 2003 to 65% in 2008. The number of ARs correlated with the number of infusions (ρ = 0.24; P < 0.001) and the average IVIg dose (ρ = 0.10; P < 0.001)., Conclusions: Low- and high-dose IVIg were safe and well tolerated with a few serious ARs in patients with neuroimmunological and immunological disorders.

Purpose: Subcutaneous immunoglobulin replacement therapy (IgRT) may be administered once a week with a pump or every other day with a syringe (rapid push). The objective of the study was to compare the impact of pump and rapid push infusions on patient's life quality index (LQI)., Methods: This study was a randomized, crossover, multicenter, non-inferiority trial conducted in adults with primary immunodeficiency (PID) accustomed to weekly infusions at home by pump. Patients used pump or rapid push for 3 months each according to the randomized sequence. Main criterion was PID-LQI factor I (treatment interference). Non-inferiority ratio was set at 90%., Results: Thirty patients entered the study; 28 completed the two periods. IgRT exposure was similar during each period. At the end of each period, mean LQI factor 1 was 87.0 (IC95% [80.3; 94.3]) and 77.80 (IC95% [71.5; 84.7]) for pump and rapid push, respectively. There was a slightly larger effect of rapid push on treatment interference than with pump so that the primary endpoint could not be met. No difference was found on other LQI components, satisfaction (TSQM), or quality of life (SF36v2). Eight patients declared to prefer rapid push while 19 others preferred pump. Of rapid push infusions, 67.2% led to local reactions vs 71.8% of pump infusions (p = 0.11) illustrating its good tolerance. Rapid push and pump infusions achieved similar trough IgG levels with similar incidence of infections. Rapid push saved 70% of administration cost when compared to pump., Conclusions: Since IgRT is a lifelong treatment in PID patients, individualization of treatment is of paramount importance. Rapid push is a new administration method in the physician's armamentarium which is preferred by some patients and is cost-effective. CLINICALTRIALS., Gov Identifier: NCT02180763 CLINICAL IMPLICATIONS: Self-administration of small volumes of immunoglobulins at home, every other day, using a syringe (rapid push) is a cost-effective alternative to administration of larger volumes by pump once a week. This study compared subcutaneous infusions of immunoglobulins either weekly via a pump or every other day via a syringe (rapid push). Rapid push is preferred by some patients and is cost-effective, therefore completing a physician's armamentarium.

Background: Hemolytic reactions (HRs) are rare serious adverse events after immune globulin (IG) use. Our large claims-based study evaluated occurrence of same-day hemolysis after administration of different IG products and potential risk factors, during the 2008 to 2014 study period., Study Design and Methods: We conducted a retrospective cohort study using a large commercial administrative database. The study included individuals exposed to IG products as identified by procedure codes. HRs were ascertained using ICD-9-CM diagnosis codes. Unadjusted same-day hemolysis rates (per 1000 persons) were estimated overall, by age, sex, and IG products. Multivariable regression analyses were used to evaluate potential risk factors., Results: Of 20,440 persons exposed, 211 (10.3 per 1000) had same-day HRs. The median numbers of doses for IG users with versus without same-day hemolysis were one and six, respectively. The unadjusted product-specific HR rates ranged from 1.92 for subcutaneous product Hizentra to 17.99 for intravenous Octagam. The multivariable regression analyses showed significantly increased same-day HR risk in males and in IG users with histories of hemolysis, pneumonia, and hereditary hemolytic anemias. Compared to Gammagard Liquid, significantly elevated overall hemolysis risk was identified with Octagam (odds ratio, 2.36; 95% confidence interval, 1.04-5.35), using Firth's method to account for small sample size bias., Conclusion: The study showed variation in the same-day IG-related hemolysis by age, sex, and IG products administered. The results suggest importance of underlying health conditions, especially prior hemolysis, and first IG product dose. Differences in HR occurrence may also be explained by product manufacturing processes, indications, routes, and rates of administration, which warrant further investigation., (© 2017 AABB.)

Background: Acute renal failure (ARF) is a rare serious adverse event after immune globulin (IG) use. Our large claims-based study evaluated occurrence of same-day ARF after administration of different IGs and ascertained potential risk factors, during the 2008 to 2014 study period., Study Design and Methods: A retrospective cohort study was conducted using a large commercial administrative database. The cohort included individuals exposed to IG products as identified by procedure codes. ARF was ascertained using ICD-9-CM diagnoses. Unadjusted same-day ARF rates (per 1000 persons exposed) were estimated overall and by age, sex, and IG products. Regression analyses were conducted to control for confounding and assess potential risk factors., Results: Of 20,440 persons exposed, 163 (7.97 per 1000) had a recorded same-day ARF. The unadjusted nonzero same-day ARF rates (per 1000) ranged from 1.92 (95% confidence interval [CI], 0.05-10.69) for Hizentra to 16.97 (95% CI, 11.36-24.37) for Privigen and differed by sex. In multivariate analyses, compared to Gammagard Liquid, no significantly elevated ARF risks were identified with any IGs. A significantly lower odds ratio was identified with Gamunex, 0.53 (95% CI, 0.30-0.93). Age 45 and over, prior renal impairment, hypertension, and other factors were associated with increased risk of same-day ARF., Conclusion: The study showed variation in the risk of IG-related ARF by age, sex, and IG products. The study results suggest the importance of recipient factors, such as older age and underlying health conditions. Variations in ARF occurrence may also be explained by product dosage, administration route and rate, and manufacturing processes, which warrant further evaluation., (© 2017 AABB.)

Patients have to be informed about the risks and benefits of medicinal products derived from human plasma. No study has examined the patient's perspective yet. Our objective was to assess perceived benefits and risks of immunoglobulins administration from the patient's point of view. Thirty-four patients receiving subcutaneous or intravenous immunoglobulins for chronic disorders at a single university hospital were asked to complete a survey. Although the level of comfort was high, the results revealed variable and incomplete knowledge, in particular about the nature of the treatment. Greater efforts should be made by health professionals to provide information to patients about plasma-derived medicinal products., (Copyright © 2017 Société française de pharmacologie et de thérapeutique. Published by Elsevier Masson SAS. All rights reserved.)

Objectives To evaluate serum-derived bovine immunoglobulin/protein isolate (SBI) for safety and impact on gastrointestinal (GI) symptoms in HIV patients with chronic idiopathic diarrhea. Methods A multi-center trial comprised of a double-blind, placebo (PBO)-controlled lead-in phase, (participants received PBO or SBI at 2.5 or 5.0 g BID for 4 weeks) followed by a 20-week, PBO-free phase (SBI at either 2.5 or 5.0 g BID). Participants included HIV-infected patients who were virologically suppressed with a history of chronic idiopathic diarrhea, defined as > 3 loose stools per day for ≥ 3 months without an identifiable cause. Safety was evaluated by monitoring adverse events (AEs) and clinical laboratory testing. Health status and changes in GI symptoms were assessed using validated questionnaires. Results SBI was well tolerated by the 103 participants with only 2 withdrawals due to AEs potentially associated with SBI. Mean number of daily unformed stools decreased from about 4 at baseline to less than 2 by week 4 for all study groups. Improvements in several other GI symptoms were also reported. Comparison of the PBO group to SBI groups showed no significant differences, although both SBI cohorts reported significantly improved health status scores. GI symptom improvements were maintained throughout the 20-week PBO-free phase. Conclusions Oral SBI is safe and well tolerated at the doses studied in HIV patients with chronic diarrhea. No conclusions could be drawn regarding impact on GI symptoms. Additional studies are ongoing to examine the biological and immunologic effects of SBI in virologically suppressed HIV-infected patients.

Background: Subcutaneous (SC) immunoglobulin (Ig) is an effective therapy for Chronic Inflammatory Demyelinating Polyradiculoneuropathy (CIDP). However, optimal dosage and frequency of administration remain to be clarified., Objectives: We sought to assess the feasibility and tolerability of a novel regimen of SCIg administration, based on concentrated "bolus" doses delivered every other week, as compared to the "conventional" SCIg regimen, based on 1-3 administrations/week., Materials and Methods: Consecutively consenting CIDP patients (6 men and 1 woman) were crossed-over from SCIg "conventional" to SCIg "bolus" and followed-up for 6months. The main endpoints were: tolerability, defined as the percentage of patients successfully completing the study, patient's perceived disability, as measured by the Rasch-built Overall Disability Scale (R-ODS), life quality index (LQI), and inflammatory neuropathy cause and treatment (INCAT) scale., Results: SCIg "bolus" was well tolerated by all patients. The R-ODS score significantly improved (p=0.042), as well as the LQI sub-domains related to the interference of treatment in daily living activities (p=0.026), and therapy-related problems (p=0.039). No significant change was observed in the INCAT (p=0.317) score. There were no cases of drop-out and/or dose adjustment during follow-up., Conclusions: SCIg "bolus" seems to represent an effective and well-tolerated option for CIDP maintenance therapy., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Objective: To investigate the efficacy, tolerability, and safety of subcutaneous immunoglobulin (SCIg) in patients with mild to moderate myasthenia gravis (MG) exacerbation., Methods: We performed a prospective, open-label, phase 3 trial in patients with MG aged 18 years or older and mild to moderate worsening (transition from Myasthenia Gravis Foundation of America class I to II/III or class II to III), treated with SCIg (2 g/kg), self-administered over 4 weeks. The primary endpoint was change in quantitative MG (QMG) score from baseline to study end at 6 weeks. Secondary endpoints included change in manual muscle testing (MMT), MG activities of daily living (MG-ADL), and MG composite (MGC) scores, as well as occurrence of adverse events, and tolerability as assessed via Treatment Satisfaction Questionnaire for Medication (TSQM)., Results: Twenty-two of 23 patients completed the study. QMG score decreased from 14.9 ± 4.1 to 9.8 ± 5.6 ( p < 0.0001), MMT score decreased from 16.8 ± 9.5 to 5.2 ± 4.5 ( p < 0.0001), MG-ADL score decreased from 9.5 ± 3.0 to 4.6 ± 3.0 ( p < 0.0001), and MGC score decreased from 17.4 ± 5.0 to 5.6 ± 4.5 ( p < 0.0001). Satisfaction by TSQM was high (79.6 ± 15.6%). Common adverse events included headache and injection site reactions. No serious adverse events occurred., Conclusions: SCIg is well-tolerated, safe, and effective in mild to moderate MG exacerbation. Comparative safety and efficacy must be established with randomized controlled trials., Classification of Evidence: This study provides Class IV evidence that in patients with mild to moderate MG exacerbation, SCIg is safe and effective in reducing MG disability measures., (© 2017 American Academy of Neurology.)

We describe six patients with cutaneous lupus erythematosus (cLE) during immunoglobulin G (IgG) treatment. Five patients were diagnosed with chronic inflammatory demyelinating polyneuropathy (CIDP) and one patient with possible CIDP. Five patients received intravenous immunoglobulin (IVIg) and one patient received subcutaneous immunoglobulin (SCIg). Skin lesions were systematically assessed by a dermatologist including skin biopsies. Patients showed disseminated erythematous plaques on several parts of the body with pre-dominance of the chest and face. Skin biopsies showed perivascular and perifollicular vacuolar inflammation, consistent with the diagnosis of cLE. There were no signs of systemic lupus erythematosus. Anti-SSA (Ro60) antibodies were found in two patients and anti-Ro52 antibodies were detectable in one patient. Symptoms improved in three patients after switching to another brand of IVIg and after use of topical corticosteroids. However, these measures did not lead to a complete resolution of the skin lesions. To achieve complete remission, IgG treatment was ceased in four patients. This led to remission of the skin lesions in two patients and to marked improvement in the other two patients. IVIg had to be restarted in two patients because of a relapse of CIDP which led to worsening of the skin lesions. In one patient with clear IVIg dependency, treatment was continued with addition of topical steroids. In the patient using SCIg, cLE was photosensitive and showed spontaneous remission. The relation of cLE with IgG treatment suggests an immunoglobulin-induced cLE. Only one report previously described the occurrence of IVIg induced cLE in a patient with common variable immunodeficiency., (© 2017 Peripheral Nerve Society.)

Background: Hepatitis B immune globulin (HBIG) has been an integral component of prophylaxis against hepatitis B virus (HBV) recurrence in liver transplantation (LT) recipients, but HBIG is costly and inconvenient to administer, prompting consideration of alternative regimens., Methods: In this retrospective cohort, we report on the success of antiviral therapy combined with a short course (in hospital only) HBIG in liver transplant recipients with HBV DNA less than 100 IU/mL pre-LT., Results: A total of 42 hepatitis B surface antigen (HBsAg) positive, human immunodeficiency virus and hepatitis D virus-negative patients with pretransplant HBV DNA undetectable to 100 IU/mL who received HBIG 5000 IU in anhepatic phase and daily for 5 days together with nucleos(t)ide analogues indefinitely yielded 1- and 3-year cumulative incidences of recurrence, defined by positive serum HBsAg, of 2.9% (upper 95% confidence interval, 19%). One patient had HBV viremia 16 months post-LT without detectable HBsAg. Both patients with either HBsAg positivity or viremia had recurrent hepatocellular carcinoma diagnosed within a month of detection. Post-LT survival was 98% and 94% at 1 and 5 years, respectively., Conclusions: We conclude that a very short course of HBIG combined with long-term antiviral therapy is highly effective in preventing HBV recurrence and should be the preferred strategy for LT recipients with undetectable or low-level viremia at time of LT.

Objective: We aimed to describe the current management and outcomes of patients with secondary immunodeficiencies (SID) on intravenous (IV) or subcutaneous (SC) immunoglobulins (IG) as maintenance therapy to prevent infections., Methods: Non-interventional, prospective study (average follow-up 20.5 months)., Results: Of the 307 SID patients (mean age 63.7±14.4 years, 52% males, in 31% IG newly initiated), 95.4% received IV IG (mean dosing interval 4.6 weeks, average dose 199 mg/kg per 4 weeks) and 4.6% were treated with SC IG (2.6 weeks, 343 mg/kg per 4 weeks). Median IG through level at first documentation was 5.8 g/L and did not differ between IV and SC treatment or between underlying malignancies. In 24.1% of patients, treatment was interrupted temporarily, over a mean of 11.6±6.3 months. In patients with newly initiated IG treatment the 82% overall infection rate prior to treatment dropped to 21% at 1 year., Conclusions: Under clinical practice conditions, IG replacement therapy in SID patients was feasible, diminished infection rates and improved quality of life. Average IG doses were relatively low. Tolerability of IV IG treatment was excellent., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objectives: Hepatitis B core antibody immunoglobulin G seropositivity is evidence of past exposure to hepatitis B virus. Donor or recipient hepatitis B core antibody positivity may pose a risk of reactivation, especially early after liver transplant. Although most centers advocate using antiviral agents plus hepatitis B immunoglobulin, some have recently relied on antivirals only as prophylaxis after liver transplant. Here, we retrospectively investigated patient survival in hepatitis B core antibody-positive recipients, comparing those treated with antivirals plus hepatitis B immunoglobulin versus antivirals alone., Materials and Methods: After Internal Review Board approval, we reviewed medical records of deceased-donor liver transplant recipients between 1995 and 2013. Demographic characteristics, transplant indication, hepatitis B core antibody status, time to death, and type of posttransplant prophylaxis were recorded. We also recorded whether donors showed hepatitis B core antibody positivity. Patients who died within 30 days of liver transplant were excluded., Results: There were 148 hepatitis B core antibody-positive recipients. Prophylaxis was given to 75 recipients after transplant: 8 (5%) received hepatitis B immunoglobulin, 22 (15%) received antivirals, and 45 (30%) received the combination. There were 34 deaths: 3 (38%) in hepatitis B immunoglobulin only, 3 (14%) in antiviral only, 8 (18%) in the combination, and 20 (27%) in no prophylaxis groups. One- and 5-year survival rates were similar for binary comparisons among prophylaxis groups (P > .05)., Conclusions: Preliminary results support the current practice of using hepatitis B immunoglobulin plus antivirals for prophylaxis after liver transplant. The similar survival benefit with the combination versus antiviral agents alone suggests equal effectivity for prophylaxis posttransplant. However, a clear benefit of antivirals was not evident in our analysis. Future larger prospective studies are warranted to identify potential benefits of using antivirals alone as prophylaxis after liver transplant and to further clarify their role as the sole prophylactic regimen.

Background: Intravenously administered immunoglobulins have multiple modes of action that are anti-inflammatory. They can therefore be beneficial in a number of autoimmune disorders., Objective: The aim of this article is to analyze and summarize studies on the administration of intravenous immunoglobulins in rheumatological diseases., Methods: A selective search and analysis of the literature was carried out related to the mode of action and efficacy of intravenous immunoglobulins in rheumatological diseases., Results and Conclusion: Intravenous immunoglobulins have a broad mode of action and can therefore be beneficial in almost all autoimmune diseases. Conditions in which they are of special benefit include immunothrombopenia (ITP), Kawasaki disease and idiopathic inflammatory myopathies. In rare situations, they may also be indicated in systemic lupus erythematosus (SLE), Sjögren's syndrome and neuropathies, catastrophic antiphospholipid syndrome (APS), scleroderma, antineutrophil cytoplasmic antibody (ANCA) associated vasculitis, pyoderma gangrenosum and scleromyxedema. Severe adverse events are rare. In view of the high costs of the therapy, intravenous immunoglobulins are mostly applied in emergency situations, as salvage therapy when other standard therapies have failed or when severe infections are a contraindication to the administration of immunosuppressants.

Immunoglobulin therapy is a key element in the management of most patients with primary immunodeficiency disease. Allergist/immunologists should be familiar with the appropriate evaluation of candidates for immunoglobulin, the characteristics of immunoglobulin products, and how to use them to provide the best care to their patients. Available immunoglobulin products appear to be equally efficacious, but they are not interchangeable. Minimizing the risk of serious adverse events and controlling minor side effects is important to ideal patient care. Immunoglobulin may be administered intravenously or subcutaneously. Individualizing the choice of immunoglobulin product, mode of administration, and site of care can optimize the clinical outcome and minimize the burden of care., (Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

This is the first report of penicillin/cephalosporin-resistant Helicobacter cinaedi arising from prolonged treatment. H. cinaedi, common among immunocompromised patients, caused recurrent bacteremia and cellulitis in a 19-year-old Japanese man with X-linked agammaglobulinemia. The minimal inhibitory concentration of these drugs was raised, which subsequently resulted in clinical failure. Prolonged suboptimal treatment may cause bacterial resistance to β-lactam antibiotics in H. cinaedi. It is possible that this resistance may have contributed to the treatment failure., (Copyright © 2016 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Despite improvements in the management of community-acquired pneumonia (CAP), morbidity and mortality are still high, especially in patients with more severe disease. Early and appropriate antibiotics remain the cornerstone in the treatment of CAP. However, two aspects seem to contribute to a worse outcome: an uncontrolled inflammatory reaction and an inadequate immune response. Adjuvant treatments, such as corticosteroids and intravenous immunoglobulins, have been proposed to counterbalance these effects. The use of corticosteroids in patients with severe CAP and a strong inflammatory reaction can reduce the time to clinical stability, the risk of treatment failure, and the risk of progression to acute respiratory distress syndrome. The administration of intravenous immunoglobulins seems to reinforce the immune response to the infection in particular in patients with inadequate levels of antibodies and when an enriched IgM preparation has been used; however, more studies are needed to determinate their impact on outcome and to define the population that will receive more benefit.

Autoimmune diseases are not infrequently associated with arterial or venous thrombotic events. Chronic inflammation and immune system impairment are considered the main pathogenetic mechanisms. Some of the drugs used in the treatment of such diseases have been associated with an increased risk of thrombosis. On the contrary, their anti-inflammatory and immune modulator activity could correct some mechanisms leading to thrombosis. In this review, recent evidence available on this topic is examined. There is a lack of adequate studies, but available evidence suggests that glucocorticoids and high-dose immunoglobulins are associated with an increased incidence of venous thromboembolism. Although available data do not allow drawing definite conclusions and more data are needed from future studies and registries, physicians should be aware of these associations., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Polyclonal plasma-derived IgG is a mainstay therapeutic of immunodeficiency disorders as well as of various inflammatory autoimmune diseases. In immunodeficiency the primary function of IVIG/SCIG is to replace missing antibody specificities, consequently a diverse Fab-based repertoire is critical for efficacy. Attempts to capture the Ig repertoire and express it as a recombinant IVIG product are currently ongoing. Likewise correction of the defective genes by gene therapy has also been tried. However, both approaches are far from becoming mainstream treatments. In contrast, some of the most important effector mechanisms relevant in therapy of autoimmunity are based on the Fc-portion of IgG; they include scavenging of complement and blockade/modulation of IgG receptors (Fc gamma receptor [FcγR] or the neonatal Fc receptor [FcRn]). These effects might be achieved with appropriately formulated Fc-fragments instead of full-length IgG, as suggested by a pilot study with monomeric plasma-derived Fc in children with ITP and in Kawasaki disease in the 1990s. Since then it has been proposed that structured multimerization of Fc fragments might confer efficacy at much lower doses than with IVIG. Accordingly, various molecular strategies are currently being explored to achieve controlled Fc multimerization, e.g. by fusion of IgG1 Fc to the IgG2 hinge-region or to the IgM tail-piece. Safety considerations will be crucial in the evaluation of these new entities. In a different approach, mutant Fc fragments and monoclonal antibodies have been designed for blockade of the FcRn., (Copyright © 2016 Elsevier B.V. All rights reserved.)