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Összefoglaló. Bevezetés: A Kawasaki-szindróma immunvasculitis, amely kezeletlenül kardiológiai szövődményekhez vezethet. A korai intravénás immunglobulin-terápia mérsékli a szövődményeket, de az esetek 10–20%-a rezisztens a kezelésre. Ennek előrejelzésére világszerte számos rizikóbecslő pontrendszert használnak. Célkitűzés: A Kobayashi- és a Kawanet-pontrendszer prediktív értékének vizsgálata betegeink intravénás immunglobulin-rezisztenciája és kardiológiai szövődményei vonatkozásában. Tudomásunk szerint ez az első magyarországi vizsgálat, amely Kawasaki-szindróma esetében pontrendszerek prediktív értékét méri fel. Módszer: Retrospektív pilotvizsgálatunkban kigyűjtöttük a 2005. január és 2020. április között Kawasaki-szindróma miatt ápolt betegeink adatait. Mindegyiküknél Kobayashi-, illetve Kawanet-pontot számoltunk, valamint megvizsgáltuk azok specificitását, szenzitivitását az intravénás immunglobulin-rezisztencia, illetve a kardiológiai szövődmények előrejelzése szempontjából. A Kobayashi-pontrendszerben 4, a Kawanet-pontrendszerben pedig 2 pont vagy annál magasabb érték jelez rizikót. Eredmények: Kawasaki-szindrómát 28 gyereknél véleményeztünk, 13 esetben észleltünk mérsékelt, 4 esetben súlyos szövődményt. 4 betegünk bizonyult intravénás immunglobulinra rezisztensnek. A rezisztencia szempontjából a Kobayashi-pontrendszer alacsony szenzitivitást (25%), illetve magas specificitást (91,6%), míg a Kawanet-pontrendszer mérsékelt szenzitivitást (50%) és specificitást (50%) mutatott. A szövődmények szempontjából hasonló eredményeket kaptunk, Kobayashi-pontrendszer: szenzitivitás: 17%; specificitás: 100%, illetve Kawanet-pontrendszer: szenzitivitás: 47%; specificitás: 45%. Következtetés: A legtöbb, nem ázsiai országban készült tanulmányhoz hasonlóan az intravénás immunglobulin-rezisztencia előrejelzésében a Kobayashi-pontrendszer vizsgálatunkban sem bizonyult hatékonynak. Ezzel szemben, magasabb szenzitivitása miatt, a Kawanet-pontrendszer intravénás immunglobulin-rezisztenciát előre jelző hatékonyságát érdemes lenne nagyobb esetszámban vizsgálni a hazai populációban is. A kardiológiai szövődmények előrejelzésére egyik pontrendszer sem bizonyult alkalmasnak. Orv Hetil. 2021; 162(47): 1885–1890. Summary. Introduction: Kawasaki disease is an immunovasculitis, which, without treatment, leads to cardiac complications. Early intravenous immunoglobulin therapy moderates complications, however, 10–20% of patients are resistant to the therapy. Numerous risk score systems are used worldwide to predict this. Objective: To assess the predictive value of the Kobayashi and Kawanet score systems regarding intravenous immunoglobulin resistance and cardiac complications in our department’s patient cohort. To our best knowledge, this is the first study in Hungary, which examines the predictive value of score systems in the case of Kawasaki disease. Method: In our study, we identified the patients treated for Kawasaki disease between January 2005 and April 2020. In each case, we calculated both the Kobayashi and the Kawanet score, and we examined their specificity and sensitivity regarding the prediction of intravenous immunoglobulin resistance and cardiac complications. In the Kobayashi score system, values above 4, in the Kawanet score system, values above 2 signal risk. Results: We identified 28 patients with Kawasaki disease. We observed moderate complications in 13, severe complications in 4 cases. 4 of our patients were resistant to intravenous immunoglobulin therapy. Regarding intravenous immunoglobulin resistance in our patient cohort, we detected low sensitivity (25%) and high specificity (91.6%) in the case of Kobayashi score, and moderate sensitivity (50%) and specificity (50%) in the case of Kawanet score. Regarding complications, we found similar results in the case of Kobayashi (sensitivity: 17%; specificity: 100%) and the Kawanet (sensitivity: 47%; specificity: 45%) score system. Conclusion: Similarly to the majority of non-Asian studies, we found the Kobayashi score system ineffective in predicting intravenous immunoglobulin resistance. However, due to its higher sensitivity, the predictive value of the Kawanet score system regarding intravenous immunoglobulin resistance is worth examining in a larger patient population in Hungary. Regarding the prediction of cardiac complications, both score systems were found to be ineffective. Orv Hetil. 2021; 162(47): 1885–1890.

Background Many clinicians are aware that certain therapies administered to their patients can have downstream consequences in the form of clinical laboratory test interferences. This is particularly true of laboratory tests that depend on, or directly involve the use of, antibody-based methodology. Intravenously-administered immunoglobulin therapy is one such treatment that can in theory directly impact the results of particular tests in the area of viral serology. This study can help serve as a reference for clinicians researching the impact of intravenously-administered immunoglobulin therapy in the context of positive results that do not reflect the clinical background of the patient. Case presentation We describe a case whereby an intravenously-administered immunoglobulin therapy led to a series of clinical false positives in viral serology, inconsistent with the known patient history as well as recent laboratory results. The patient presented to hospital with petechiae-type bleeding rashes and was investigated for thrombocytopenia after initial blood investigations indicated very low platelets. Subsequent testing of the potential causes for low-platelet involved several viral serology investigations, including hepatitis, cytomegalovirus and human immunodeficiency virus. Initial testing indicated patient exhibited negative status for all viral antibodies and antigens (except immunity for hepatitis B surface antigen antibody). As part of the thrombocytopenia treatment, intravenously-administered immunoglobulin therapy was administered, and subsequent viral serology was ordered. These investigations indicated a positive status for several hepatitis antibodies as well as cytomegalovirus. Conclusions This case study illustrates the potential for improper diagnosis of previous or ongoing infection status in patients administered IVIg therapy. Caution should be exercised particularly when interpreting results involving cytomegalovirus and hepatitis.

Histobulin is complementary to IVIG therapy but is an essential therapeutic for PWCD. Histoublin is recommended not only in atopic dermatitis and multiple food allergies but also in patients with multiple allergic diseases.

Background Patients whose parents had a history of Kawasaki disease (KD) often show a poor response to intravenous immunoglobulin (IVIG). There are very few reports describing the clinical characteristics and no reports on changes in C-reactive protein (CRP) level after IVIG administration in such cases. Methods A single-center cohort study including 950 patients hospitalized for KD and treated with IVIG was conducted. The patients were divided into two groups: patients whose parents had a history of KD (PHK, N=16) and patients whose parents had no history of KD (NPHK, N=934). The clinical characteristics and responsiveness to IVIG were compared between the two groups. Results The PHK group had higher CRP levels before administering IVIG than the NPHK group (P=0.0010). CRP levels after IVIG administration were higher in the PHK group than in the NPHK group (P=0.0094). The percentage of patients who received a second administration of IVIG on day 2 after the initial IVIG therapy was higher in the PHK group than in the NPHK group (P=0.0016). The percentage of patients who required plasma exchange therapy in the PHK group was significantly higher than that in the NPHK group (P=0.0010). Conclusions Patients in the PHK group had severe KD before IVIG administration, and these patients showed poor responsiveness to IVIG therapy.

Stiffperson syndrome (SPS) is one of the rarest neurological disorders. It is an autoimmune disease with antibodies against glutamic acid decarboxylase - enzyme needed to produce neurotransmitter GABA. This disease is very debilitating and fatal if not managed in time. A 32-year-old man presented with stiffness of abdominal and thoracolumbar paraspinal muscles first noticed 10 months back. There was history of jerkiness of hands. After excluding other mimicking conditions like multiple sclerosis, parkinsonism and axial dystonia, a diagnosis of Stiffperson syndrome was made. Treatment with IVIG therapy along with anti-spasticity drugs resulted in improved patient outcome. SPS is potentially treatable though cannot be cured. Not one treatment fits all patients with SPS and may have to be tailored according to the clinical manifestations. Increasing awareness in medical doctors and identifying the disease early can help the patients escape the disabling effects of SPS and improve the quality of life.

Background Symptomatic COVID-19 cases in children occur mostly in those with primary immunodeficiency (PID), chronic lung diseases, and heart disease. Guidelines recommend that patients with PID continue to use their regular medication during the pandemic. Objectives This study aimed to evaluate anxiety related to COVID-19 in the parents of patients receiving intravenous immunoglobulin (IVIG) treatment in our hospital and to evaluate the effect of their anxiety on the continuity of treatment. Methods The parents of the patients who underwent IVIG therapy in our clinic during the pandemic (between May 15, 2020 and July 1, 2020) were included in our study. Results Twenty-seven patients with PID whose IVIG therapy was initiated before the pandemic and 29 non- PID control subjects were included in the study. All patients received IVIG treatment in our clinic continued treatment during the pandemic at the same dose intervals. Parents in the IVIG group had significantly higher state (p=0.003) and trait (p=0.003) anxiety scores compared to control parents. IVIG group showed statistically significant higher scores in Beck depression inventory, than the control group (p=0.002). Conclusions The parents of PID patients who needed to come to the hospital for IVIG therapy had higher anxiety levels than the parents of similar aged children who presented to our clinic for different complaints between the same dates. Despite their concerns, the parents of all patients under IVIG therapy maintained treatment continuity at the recommended treatment intervals. None of our immunodeficient patients who presented for treatment during the pandemic contracted COVID-19 infection during our study.

Background Immunoglobulin replacement has been standard therapy for patients with primary immunodeficiency diseases (PIDD). Intravenous immunoglobin (IVIg) is delivered at the hospital, whereas subcutaneous immunoglobin (SCIg) is used for home-based treatment. The aim of the study was to determine the advantages and disadvantages of IVIg and SCIg in Polish children aged 1-5 years, with PIDD, and the satisfaction of their parents / caregivers regarding immunoglobulin replacement. Methods The research involved parents of 23 children with PIDD, aged 1-5 years. All children were given IVIg therapy and after at least 6 months they were switched towards home SCIg therapy for at least 6 months. A questionnaire assessing advantages and disadvantages of preferred types of treatment and the quality of life of PIDD patients' families' lives was used. Results The research showed that IVIg therapy was better accepted by parents than SCIg therapy (P = 0.034) for the following reasons: It made it possible for the children to receive treatment once per month (60%); it reduced the fear of injecting the children (60%), and it provided better control of the disease through regular visits to the hospital (53.33%). Parents noticed, however, that IVIg had a significant impact on absence at school or work (70%). Parents who preferred SCIg for their children were guided mainly by the smaller number of side effects (40%), and the fact that the treatment did not interfere with parents' work or the children's school (40%). Conclusion The results showed that IVIg therapy was better accepted by parents than SCIg therapy Parents of children with SCIg are less satisfied with their life, and feel anxiety about their children disease, which is related to administering the medicine by themselves.

Background: Infants younger than 1 year of age with Kawasaki disease (KD) have a high risk for coronary artery lesions (CAL). However, the appropriate acute phase treatment for the infants has not been established. Objective: To ascertain the usefulness of an initial single intravenous immunoglobulin (IVIG) therapy (2g/ kg) with delayed use of aspirin (DUA) for the infants. Materials and Methods: The outcomes in 205 patients who underwent initial single IVIG therapy at 2g/ kg/ dose with DUA for KD were investigated retrospectively. These subjects were divided into those aged

Jeffrey T Guptill,1 M Chris Runken,2 Michael Eaddy,3 Orsolya E Lunacsek,4 Rupali M Fuldeore,4 Christopher M Blanchette,5 Emily Zacherle,5 Joshua M Noone51Department of Neurology, Duke University, Durham, NC, USA; 2Grifols SSNA, Research Triangle Park, Durham, NC, USA; 3Scientific Consulting, Xcenda, Palm Harbor, FL, USA; 4Real-World Evidence, Xcenda, Palm Harbor, FL, USA; 5Department of Public Health Sciences, University of North Carolina at Charlotte, Charlotte, NC, USAPurpose: For chronic inflammatory demyelinating polyneuropathy (CIDP) patients, each branded intravenous immunoglobulin (IVIG) treatment differs in production processes, virus elimination, formulation, and composition. Given the limited availability of real-world data comparing IVIGs for CIDP, this study evaluated switching patterns between IVIG products in 2 separate retrospective databases.Patients and methods: Two independent analytic teams retrospectively evaluated IVIG treatment-naïve patients with an ICD diagnosis code for CIDP. Study 1 used integrated healthcare claims from IMS LifeLink PharMetrics Plus™ and Study 2 used the Truven MarketScan® Database. All analyses were descriptive, with outcomes assessed during the 2-year post-index period.Results: One-quarter of IVIG patients switched therapies within the 2-year study period. In both studies, switching rates were lowest for IVIG-G (Gamunex®-C) (Study 1: 9.8%, Study 2: 8.9%), followed by IVIG-F (Flebogamma®) (Study 1: 25.0%, Study 2: 18.2%), and highest for IVIG-other (Octagam®/Gammaplex®) (Study 1: 50.0%, Study 2: 33.3%). When patients were switched, most switched to IVIG-G (Study 1: 51.6%, Study 2: 54.3%).Conclusion: The small proportion of CIDP switchers in 2 independent studies suggests that IVIG therapy is generally well tolerated. However, differences existed in switch rates for different IVIG products. The reason for low switching rates could not be assessed in this study; therefore, further studies are required to detect possible relevant differences in effectiveness and tolerability.Keywords: intravenous immunoglobulin, chronic inflammatory demyelinating polyneuropathy, treatment patterns

Introduction: Kawasaki disease is a common systemic vasculitis of unknown cause in children and involves various organs but the main damage of this multisystemic vasculitis is mainly in the coronary arteries. Currently, the main treatments for this disease include aspirin therapy and IVIG. In the present study, we investigated the ratio of neutrophils to lymphocytes in patients with Kawasaki disease and its relationship with IVIG resistance in Kawasaki patients.Method: First, we reviewed the clinical records of patients diagnosed with Kawasaki, who received treatment at Motahari Hospital in Urmia from 2008 to 2018 (IVIG therapy). We re-examined Kawasaki diagnostic criteria for each individual before enrolling patients. Results: In our study, initially 460 cases of patients who were admitted to Motahari Hospital in Urmia between 2009 and 2019 with an initial diagnosis of Kawasaki disease were reviewed. Among them, patients who met Kawasaki diagnostic criteria were included in the final review and the rest of the cases were excluded from the study according to the exclusion criteria. Finally, out of 460 cases, 241 patients were included in the final analysis. The results indicated high blood leukocyte count (p-value = 0.013) and low urinary leukocyte count (p-value = 0.01) were directly related to response to treatment in Kawasaki patients, but age, sex, neutrophil ratio to Lymphocytes, neutrophil count, blood lymphocytes, CRP, hypoalbuminemia, ALT levels, anemia, thrombocytosis, and the time interval between onset of symptoms and treatment response to IVIG therapy in Kawasaki patients are not significantly related.Conclusion: High blood leukocyte count and low urinary leukocyte count in patients can be good criteria for predicting the prognosis of Kawasaki patients in response to IVIG, while the ratio of neutrophils to lymphocytes is not effective in this prediction.

International audience; Intravenous immunoglobulin (IVIG) is used to treat several autoimmune and inflammatory diseases, but some patients are refractory to IVIG and require alternative treatments. Identifying a biomarker that could segregate IVIG responders from non-responders has been a subject of intense research. Unfortunately, previous transcriptomic studies aimed at addressing IVIG resistance have failed to predict a biomarker that could identify IVIG-nonresponders. Therefore, we used a novel data mining technique on the publicly available transcriptomic data of Kawasaki disease (KD) patients treated with IVIG to identify potential biomarkers of IVIG response. By studying the boolean patterns hidden in the expression profiles of KD patients undergoing IVIG therapy, we have identified new metabolic pathways implicated in IVIG resistance in KD. These pathways could be used as biomarkers to segregate IVIG nonresponders from responders prior to IVIG infusion. Also, boolean analysis of the transcriptomic data could be further extended to identify a universal biomarker that might predict IVIG response in other autoimmune diseases.

Although the treatment of the hyperinflammatory response due to COVID-19 has not yet been found, high-dose corticosteroids, interleukin receptor blockers and intravenous immunoglobulin (IVIG) are used to improve the hyperinflammatory response. In this article, we aimed to share our experiences with 3 patients who received IVIG therapy in ICU. (English) [ABSTRACT FROM AUTHOR] COVID-19’a bagli gelisen hiperinflamatuvar yanitin kesin bir tedavisinin henuz bulunamamis olmasina ragmen, yuksek doz kortikosteroid, interlokin reseptor blokerleri ve intravenoz immunoglobulin (IVIG) tedavisi bugunlerde kullanilmaktadir. Biz bu makalemizde, yogun bakimimizda IVIG tedavisi uyguladigimiz 3 Covid-19 hastasindaki tecrubelerimizi paylasmayi amacladik. (Turkish) [ABSTRACT FROM AUTHOR] Copyright of Anestezi Dergisi (JARSS) is the property of Logos Medical Publishing and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Coronavirus disease 2019 (COVID-19) pandemic has drawn attention over old immunotherapeutic agents such as convalescent (immune) plasma (CIP). Here, an adolescent with severe COVID-19 case requiring CIP and intravenous immunoglobulin (IVIG) treatments is described. A 17-year-old male patient was brought to the emergency room with complaints of fever, fatigue, and severe cough. Two doses of CIP were infused to the patient because of the increase in persisting fever, dyspnea, and acute phase reactant levels after the third day of routine protocol treatment. IVIG therapy was begun for 2 days at a dose of 1 g/kg/day due to resurgence in acute phase reactants and progressing radiological findings following CIP transfusion. Our patient avoided mechanical ventilation and showed immediate clinical and radiological improvement with CIP transfusion followed by IVIG therapy. Timely initiation of CIP treatment followed by IVIG prevented the disease from worsening and helped to reduce the requirement for mechanical ventilation.

The outbreak of a severe acute respiratory syndrome caused by a novel coronavirus (COVID-19), has raised health concerns for patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), who are frequently on long-term immunotherapies. Treatment with IVIg does not increase the risk of contracting COVID-19, and the IVIg administration may have a protective role. However, infusions can expose patients to an increased risk of contracting SARS-CoV-2 due to repeated access to Health Facilities. In this report we analyzed the short-term follow-up of CIDP patients who modified their chronic IVIg therapy during pandemic. About half of CIDP patients regularly treated with IVIg tried to stop treatment and about 10% shifted to SCIg. Forty-two percent of the patients who stopped the treatment reported a clinical deterioration after suspension and had to restart IVIg. This study demonstrated that in selected cases it is possible to successfully stop the chronic IVIg treatment, even in patients who have been treated for several years.

Intravenous immunoglobulin (IVIG) is a standard therapy for Kawasaki disease (KD), because it prevents formation of coronary artery aneurysm, a major complication of KD. Herein, we report a 3-year-old boy with KD complicated by haemolytic anaemia (HA) which developed following two courses of IVIG. Although both direct and indirect antiglobulin tests and anti-M antibodies were positive in his blood obtained after the onset of HA, indirect antiglobulin tests and anti-M antibodies were negative either in the blood sample before the treatment or the same lot of IVIG products as those used for the therapy, suggesting autoimmune mechanism. This is, to our knowledge, the first report of autoimmune HA caused by anti-M autoantibodies after IVIG therapy in KD.

A steroid- and cyclosporine A- resistant case of Pfeiffer-Weber-Christian disease (PWCD) was remitted completely with sequential treatment with Histobulin and IVIG. The multiple food allergies and the atopic dermatitis of this PWCD patient were also improved with Histobulin treatment. The upper respiratory infections were improved by Histobulin therapy also.

Intravenous immunoglobulin (IVIg) is increasingly used for the treatment of inflammatory and autoimmune diseases. Although skin reactions to IVIg therapy are usually minor, rare, and not life-threatening, dermatologists need to recognize the nature of these adverse reactions. We describe a 33-year-old man suffering from demyelinating polyneuropathy who developed dyshidrotic eczema on the palms and flaky grayish-white scales on an erythematous base on his face after the administration of IVIg.

Intravenous immunoglobulin (IVIG) is an immune modulating treatment used in a variety of immune mediated diseases. We report, two patients of different demographics, treated with IVIG for different neurological diagnoses who reported significant hair growth after starting IVIG treatments. To date, there have been no reports of using IVIG as a treatment for hair loss due to androgenic alopecia (AGA).

ObjectiveEpidemics of Kawasaki disease (KD) are well known; however, the seasonal variation in the clinical course of KD is uncertain. The aim of this study was to investigate the seasonality in the clinical course of KD.MethodsThis study included 744 patients who were admitted to six hospitals in Kitakyushu City for KD from 2010 to 2014. We divided the patients into two groups according to the average monthly temperature (warm and cold periods) and compared the clinical courses of KD.ResultsThe clinical courses of 715 patients who were initially treated with intravenous immunoglobulin (IVIG) were investigated. The proportion of patients with resistance to the initial IVIG therapy was significantly higher during the warm period than during the cold period (p=0.016). There was no seasonality in the proportion of patients with coronary artery abnormalities.ConclusionSeasonality was observed in the response to IVIG therapy of patients with KD.

Background Intravenous immunoglobulin (IVIG) is prepared using purified human plasma. IVIG therapy has immunomodulatory effects on autoimmune diseases, including severe systemic lupus erythematosus (SLE). However, reports of its effects on large cohorts are scarce. Methods This single-center retrospective study included SLE patients treated with at least one IVIG cycle for SLE complications. Demographic data, indications, cycle numbers, and clinical improvement with IVIG were evaluated. SLE Disease Activity Index 2000 (SLEDAI-2K) scores were calculated at admission and after IVIG treatment in order to measure clinical improvement. Results Sixty-three SLE patients treated with IVIG (median age: 29 years; interquartile range 21–36 years; 84.13% female) were included, who received 2 g/kg IVIG for two to five days. Main indications were immune thrombocytopenia, hypogammaglobulinemia, infection during a SLE flare, bicytopenia, and immune hemolytic anemia. Seven patients received more than one IVIG cycle without severe adverse effects. Significant differences were found in SLEDAI-2K scores when the indications were immune thrombocytopenia and hypogammaglobulinemia, with a trend for hemolytic anemia. Patients with concomitant infection, myopathy, and gastrointestinal involvement showed a considerable reduction in their last SLEDAI-2K scores. Fourteen patients died during hospitalization, mainly due to septic shock and active SLE. Conclusions IVIG showed adequate tolerance and effectiveness in selected severe SLE manifestations, mainly hematological involvement. It was useful for concomitant infection.

BACKGROUND Evidence suggests that seasonal variation in the onset of Kawasaki disease (KD) exists worldwide. Whether a seasonal component to successful i.v. immunoglobulin (IVIG) therapy exists in KD-positive children, however, is unknown. We addressed this question by focusing on patients with primary onset KD who were non-responsive to IVIG treatment, in the large nationwide Japanese KD survey datasets from 2009 to 2016. METHODS In these datasets, the IVIG therapy non-responders were defined as patients whose fever persisted ≥24 h or recurred ≤24 h after the end of the initial IVIG treatment (dosage, 2,000 mg/kg). Those who successfully responded to this treatment were defined as IVIG responders. The consecutive monthly trend of the proportion of IVIG non-responders was analyzed throughout the study period to investigate seasonal periodicity on Fourier analysis, and the monthly distributions of non-responders and responders were compared. RESULTS From a total of 113 691 KD-positive patients, 15.7% were IVIG non-responders, and 61% were male. The proportion of non-responders increased across each calendar year with fluctuation, and Fourier analysis indicated seasonal periodicity. The seasonality effect differed between responders and non-responders, with the proportion of responders tending to increase in autumn through winter, while the non-responders showed a decreasing trend in autumn. The seasonality effect tended to differ by sex. CONCLUSIONS The results indicate that the currently unknown etiological agents of KD might differ between IVIG responders and non-responders. In addition, immune reactivity against such agents possibly differs by sex in the IVIG non-responders.

IntroductionBased on data obtained before high-dose (2 g/kg) intravenous immunoglobulin (IVIG) therapy prevailed in Japan, children with a history of Kawasaki disease (KD) were highly susceptible to disease recurrence and more likely to develop cardiac sequelae. We aimed to examine the epidemiological features of cardiac complications among patients with recurrent KD following the widespread use of high-dose IVIG therapy.DesignTwo cohorts of patients with recurrent KD retrieved from Japanese nationwide surveys (previous cohort: 1989–1994; recent cohort: 2003–2012) were compared.ResultsOf 1842 patients with recurrent KD in the recent cohort, 3.5% and 5.2% developed cardiac sequelae at the initial and second episodes, respectively, which were markedly decreased compared with those (>10%, respectively) in the previous cohort. Multivariate analyses showed that the risk factors for cardiac sequelae at the second episode were similar between the cohorts. Patients with recurrent KD in both cohorts were more likely to have coronary aneurysms at the second episode than at the initial episode. However, when patients with coronary aneurysms at the initial episode were excluded from analyses, the difference in the proportions of coronary aneurysms between KD episodes disappeared in the recent cohort. Residual rates of previously formed coronary aneurysms were similar between the cohorts (approximately 50%).ConclusionThis study suggests that KD recurrence is no longer a risk factor for developing cardiac complications, unless cardiac sequelae appear at the initial episode. However, residual rates of previously formed coronary aneurysms remain high. Therefore, the importance of carefully managing coronary aneurysms associated with KD remains unchanged.

Kawasaki disease (KD) has complexly clinical features and laboratory parameters and there is no definitive biomarker for this disease and the therapy of KD also is complex and uncertain. In this study, 102 KD patients and 80 healthy controls were enrolled in this study and the serum microRNAs were detected by qRT-PCR. The results showed that, compared with KD patients with a good response to high-dose intravenous immunoglobulin (IVIG) therapy, serum miR-200c and miR-371-5p were significantly higher in KD patients with no response to IVIG therapy; compared with KD patients not needing plasma exchange, these two microRNAs were also significantly higher in KD patients needing plasma exchange. In addition, combination of serum miR-200c and miR-371-5p reflected obvious separation between KD patients and healthy controls or between KD patients with no response to IVIG therapy and KD patients with good response to IVIG therapy or KD patients needing plasma exchange and KD patients not needing plasma exchange. Finally, both serum miR-200c and miR-371-5p were also significantly lower in KD under different kinds of therapy. Therefore, serum miR-200c and miR-371-5p have ability as the useful diagnostic biomarkers and therapeutic targets in Kawasaki disease.

We report a case of a male patient with Emanuel syndrome (ES) with multiple systemic malformations. He had frequent recurrent seizures and infectious diseases after six months. Because the level of immunoglobulin (IgG) was below the normal range for his age, he was administered intravenous immuno-globulin (IVIG) whenever infection occurred. As he grew up, the frequency of infections and seizures were reduced after IVIG therapy. Although the mechanism was not identified, IVIG might be effective for not only recurrent infections, but also for reducing recurrent seizures.

The objective of this study is the description of clinical outcomes regarding the absence of rescue therapy of intravenous immunoglobulin (IVIG)-resistant Kawasaki disease. I investigated the clinical outcomes of 33 IVIG-resistant patients who received the initial single IVIG therapy with the delayed use of anti- inflammatory drugs (DUA). These patients were divided into two groups: 11 patients who received rescue therapies (rescue group) and 22 patients who did not receive rescue therapy (non-rescue group). One patient of rescue group developed coronary artery lesions (CAL). None of the patients of non-rescue group developed CAL. The prevalence of persistent fever between rescue and non-rescue groups at 3 days and 4 days after initial IVIG therapy was 100% vs. 77% ( P = 0.144 ) and 100% vs. 18% ( P < 0.001 ), respectively. The C-reactive protein value, neutrophil counts, serum albumin levels, and sodium levels were significantly different between two groups at median 3 days after initial IVIG therapy. Two-thirds of the IVIG-resistant patients diagnosed at 24 h after completion of the initial IVIG therapy with DUA did not develop CAL after 30 days of illness without rescue therapies. The rescue therapy at this time may lead to overtreatment.

BackgroundThis project is an effort to understand how orders for IV immunoglobulin (IVIg) are documented and prescribed by physicians, and subsequently, how they are reviewed by insurance companies for the treatment of immune neuropathies.MethodsA panel of neuromuscular specialists reviewed case records from 248 IVIg-naive patients whose in-home IVIg infusion treatment was submitted to insurance for authorization. After reviewing a case record, 1 panelist was asked to make a diagnosis and to answer several questions about the treatment. A second panelist reviewed the original record and follow-up records that were obtained for reauthorization of additional treatments and was asked to determine whether the patient had responded to the treatment.ResultsOur specialists believed that only 32.2% of 248 patients had an immune neuropathy and were appropriate candidates for IVIg therapy, whereas 46.4% had neuropathies that were not immune mediated. Only 15.3% of cases met electrodiagnostic criteria for a demyelinating neuropathy. Our specialists believed that 36.7% of 128 cases with follow-up records had responded to therapy. In cases in which the initial reviewer had predicted that there would be a response to IVIg, the second reviewer found that 54% had responded. This is compared with a 27% response rate when the first reviewer predicted that there would be no response (p = 0.019).ConclusionsOur expert review finds that the diagnosis of immune neuropathies made by providers, and subsequently approved for IVIg therapy by payers, is incorrect in a large percentage of cases. If payers include an expert in their review process, it would improve patient selection, appropriate use, and continuation of treatment with this expensive therapeutic agent.

At 37 years of age, the patient initially presented with symptoms of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) during her 1st pregnancy. She was treated with intravenous immunoglobulin (IVIg), and showed favorable recovery, becoming almost asymptomatic by the age of 38. At 39 years of age, during her puerperal period of her second pregnancy, she developed symmetrical muscle weakness and sensory disturbance of the upper and lower limbs. Nerve conduction studies revealed diffuse demyelination of peripheral nerves, and she was diagnosed with recurrence of CIDP. Once again, she showed remarkable improvement after IVIg therapy, and she has remained asymptomatic without the induction of preventative therapies. Recurrence of CIDP triggered in accordance with multiple pregnancies is extremely rare, and its clinical and electrophysiological features are presented in this report.

This is a case series describing 12 youths treated with intravenous immunoglobulin (IVIG) for pediatric autoimmune neuropsychiatric disorder associated with streptococcal infection (PANDAS). Although it is a clinically based series, the case reports provide new information about the short-term benefits of IVIG therapy, and are the first descriptions of long-term outcome for PANDAS patients.

Background There is still no definite treatment for refractory Kawasaki disease (KD). In this pilot study, we evaluated the safety and efficacy of a new protocol consisting of sivelestat sodium hydrate (SSH) combined with additional i.v. immunoglobulin (IVIG) for KD resistant to initial IVIG therapy. Methods This study is a prospective non-randomized, open-label and single-arm study undertaken in a population of refractory KD patients at Chiba University Hospital from December 2006 to March 2016. The subjects had KD resistant to initial IVIG (2 g/kg) and received SSH (0.2 mg/kg/h for 5 days) combined with additional IVIG (2 g/kg) as a second-line therapy. We evaluated the safety and efficacy of the treatment during the study period. Results Forty-six KD patients were enrolled in this study and no serious adverse event was noted. Of these, 45 patients were evaluated for the incidence of coronary artery lesions, which occurred in one patient (2.2%; 95% CI: 0.5-15.2). Twenty-eight (62.2%) responded promptly and were afebrile after the therapy. The median total duration of fever was 8 days (range, 6-28 days). Conclusions Additional IVIG combined with SSH as a second-line therapy for KD refractory to initial IVIG therapy was safe and well tolerated and could be a promising option for severe KD. Further investigations are expected to clarify the safety and timing of SSH treatment for KD.

RIF (repeated implantation failure) women with immunologic basis and cellular abnormalities may benefit from intravenous immunoglobulins (IVIG) as an immunomodulator based on different studies. In this study, we evaluated the effect of IVIG on the frequency and function of Th17 and Treg cells, as two important subgroups of CDRIF: repeated implantation failure; IVIG: intravenous immunoglobulin; Th17: T helper 17; Treg: T regulatory; NK cells: natural killer cells; PCR: polymerase chain reaction; ELISA: enzyme-linked immunosorbent assay; RORγt: RAR-related orphan receptor gamma; Foxp3: forkhead box protein P3; IL-17: interleukin-17; LMWH: low-molecular weight heparin; dNK: decidual NK cells.

Intravenous immunoglobulin (IVIG) replacement therapy has been used in immune deficiency diseases for more than 50 years. The indications for this treatment have evolved, however, and IVIG therapy is now used in various diseases in which the immune system plays a prominent role. IVIG therapy has carved out a niche in dermatology for the treatment of such conditions as dermatomyositis, autoimmune bullous diseases, and toxic epidermal necrolysis. Special attention has been paid to this therapy in recent years. New guidelines have been published and should be taken into consideration in dermatology. This review provides a practical guide to IVIG use in our specialty.

We examined seizure, cognitive, and motor outcomes in patients with Rasmussen syndrome or Rasmussen encephalitis (RS), after recent initiation of immunomodulatory therapies. Among 53 patients with a diagnosis of RS referred from all over Japan, 49 patients (male 22, female 27) with symptoms and findings characteristic of RS were evaluated. Regular intravenous immunoglobulin (IVIg) therapy was administered at a dose of 100 mg/kg/day, etc. Regular steroid pulse therapy was conducted with methylprednisolone at a dose of 30 mg/kg/day (children) or 1000 mg/day (adults) for 3 days. Tacrolimus was given at an initial dose of 0.1 mg/kg/day (children). Mean onset age was 8.7 ± 10.5 years. Seizure-free rate was 71% after treatment by functional hemispherectomy (FH), and response rate for seizures was 81% by regular steroid pulse therapy, 42% by tacrolimus therapy, and 23% by regular IVIg therapy. Rate of patients with IQ higher than 80 (R80) was 50% by regular steroid pulse therapy, 43% by regular IVIg therapy, 29% by tacrolimus therapy, and 0% by FH. R80 after regular steroid pulse therapy was 100% in patients without MRI lesions, and 37% in those with advanced MRI lesions. Improvement of motor function (paresis) was observed only by immunomodulatory therapy. Motor function was aggravated in 100% of patients treated by FH, 62% by regular IVIg, and 10% by regular steroid pulse therapy. We suggest a new treatment strategy for RS using early immunomodulatory therapy: initiation of regular steroid pulse therapy after early diagnosis indicated by biomarkers, then switching to tacrolimus therapy after several months.

Background: Kawasaki disease is treated by immunoglobulin therapy, which has adverse side effects like renal damage. Aims: The aim of the present study was to explore the effectiveness of triptolide, a compound derived from threewingnut that has anti-inflammatory effects, on the treatment of Kawasaki disease in a mouse model. Study Design: Animal experiment. Methods: A mouse model of Kawasaki disease was established through exposure to Candida albicans by intraperitoneal injection. Exposed mice were then randomly divided into several groups (each n=15): model group (saline-treated), low- or high-dose triptolide groups (0.2 mg/kg or 0.4 mg/kg, respectively), and IVIG (high-dose immunoglobulin) group (1 g/kg body weight). Unexposed mice served as an additional control group. Nine weeks from the initial exposure, mice were euthanised and coronary tissues and blood samples were harvested. The rate of apoptosis was detected by TUNEL, and ICAM-1 expression was detected by immunohistochemistry in coronary endothelial cells. Serum TNF-α levels were detected by ELISA. Results: Compared to mice in the (unexposed) control group, apoptosis of endothelial cells, ICAM-1 expression, and serum TNF-α levels were significantly increased in all exposed mice (p

Introduction Recurrent optic neuritis neuritis (rON) is an autoimmune inflammatory condition of unknown cause. Intravenous immunoglobulin (IVIg) treatment is used for many autoimmune disorders; however we do not have any information about its effect in rON, other than case reports. We aimed to evaluate our patients with rON who were treated with IVIg. Methods Data from all our patients with rON with or without anti aquaporin4 (AQP4) seropositivity, seen between April 2011 and October 2015, who received IVIg treatment were retrospectively evaluated. Results Nine patients (all female) with rON had received IVIg. These patients were aged between 34 and 65 years, and had started receiving monthly IVIg from 6 to 58 months after onset of disease. In three out of nine rON patients serum AQP4 antibody were positive. Under current treatments the patients had continued to have attacks, therefore monthly IVIg was given in addition to the existing immunosuppressant drug. The follow up duration was between 6 to 31 months. Three patients, each suffered one relapse under IVIg treatment. Mean number of relapses in the year prior to treatment was 1.4±0.72, whereas it was 0.3±0.5 during the year after IVIg therapy. During follow-up with IVIg administration only one patient had fever and no other adverse events were reported. Conclusion Monthly IVIg is well-tolerated and safe and it seems to be effective in rON as an add on treatment. However, since our study is a retrospective case series, future randomized controlled trials with IVIg are needed.

The management of antibody-mediated rejection in renal transplant recipients involves plasmapheresis with IVIG. Aseptic meningitis is a rare adverse effect of IVIG therapy and is a diagnosis of exclusion. We report a case of a renal transplant patient who developed IVIG associated aseptic meningitis in the context of management of antibody-mediated rejection, four years after transplantation.

Intravenous immunoglobulin (IVIg) is increasingly used for the treatment of autoimmune and systemic inflammatory diseases with both licensed and off-label indications. The mechanism of action is complex and not fully understood, involving the neutralization of pathological antibodies, Fc receptor blockade, complement inhibition, immunoregulation of dendritic cells, B cells and T cells and the modulation of apoptosis. Areas covered: First, this review describes the pharmacological properties of IVIg, including the composition, mechanism of action, and adverse events. The second part gives an overview of some of the immune-mediated polyneuropathies, with special focus on the pathomechanism and clinical trials assessing the efficacy of IVIg. A literature search on PubMed was performed using the terms IVIg, IVIg preparations, side effects, mechanism of action, clinical trials, GBS, CIDP. Expert opinion: Challenges associated with IVIg therapy and the treatment possibilities for immune-mediated polyneuropathies are discussed. The availability of IVIg is limited, the expenses are high, and, in several diseases, a chronic therapy is necessary to maintain the immunomodulatory effect. The better understanding of the mechanism of action of IVIg could open the possibility of the development of disease-specific, targeted immune therapies.

Three weeks after single-lung transplantation for pulmonary fibrosis, a patient with high serum levels of de novo donor-specific antibodies received high-dose intravenous immunoglobulin (IVIG) infusion (scheduled dose: 2 g/kg on 2 days) to prevent antibody-mediated rejection. Within the first hours after completion of infusions, he experienced acute lung injury involving the transplanted lung. Given the clinical evolution and the absence of an alternative diagnosis, transfusion-related acute lung injury (TRALI) was diagnosed. The IVIG administered on each day was from the same batch. At day 110, because of an increase in the serum titers of donor-specific antibodies, IVIG therapy was reintroduced but from a different batch, with excellent clinical tolerance. The lung injury was explored biologically, but no mechanism was revealed. Given the increasing use of IVIG in solid-organ recipients, clinicians should be aware of possible TRALI after IVIG infusion.

For more than 30 years, intravenously administered immunoglobulins (ivIG) have been used to treat primary and secondary syndromes of immune deficiency. Increasing insight into pathomechanisms of severe sepsis and septic shock have led to the implementation of ivIG therapy in the strategies for adjunctive therapy in sepsis in both adults and children. Direct antitoxic effects, as well as indirect immunomodulatory mechanisms of ivIG have been described in the literature and were the basis for the rationale to use these substances in life-threatening infections and hyperinflammatory states. Several clinical trials have been performed, most of them as minor, investigator-initiated protocols. This review summarizes the results of clinical investigations and systematic meta-analyses that have implications for the development of therapeutic strategies, and international guidelines for the management of severe sepsis and septic shock in adult patients.

Introduction Intravenous immunoglobulin (IVIG) is used to treat many inflammatory and autoimmune disorders and although generally well tolerated, cutaneous side effects occur. Objective We reviewed reports of pompholyx and eczematous reactions associated with IVIG. Methods A literature search was performed using the PubMed and MEDLINE databases with the search terms "intravenous immunoglobulin pompholyx," "intravenous immunoglobulin eczema," "intravenous immunoglobulin cutaneous adverse effects," "intravenous immunoglobulin cutaneous effects," "intravenous immunoglobulin skin effects," and "intravenous immunoglobulin adverse effects." Relevant English-language articles or articles in other languages cited in English-language articles were included. Results We identified 64 cases of eczematous reactions associated with IVIG therapy, including a patient treated on our inpatient consult service. In reported cases, the majority of patients (62.5%) had pompholyx alone or a combination of pompholyx on the hands or feet and two or fewer additional body surfaces involved. The majority of reported cases (75%) experienced the eczematous reaction after their first IVIG treatment. Neurologic conditions were the most common (85.9%) diseases for which IVIG was used. Most patients responded well to topical steroids or did not require treatment. Limitations Some reported cases had insufficient descriptions to be included in this review. A literature review may underestimate the frequency of eczematous reactions to IVIG because these reactions are often limited and may not be reported. Conclusions With the use of IVIG increasing, it is important for dermatologists to recognize this cutaneous side effect of IVIG.

In a subgroup of patients suffering from atopic dermatitis (AD), treatment is quite difficult even after taking oral immunosuppressants. High-dose intravenous immunoglobulin (IVIG) treatment has been reported to be beneficial for them in a few uncontrolled trials. Herein we report a case of intractable AD in a 5-year-old girl who had significant clinical improvement after receiving 3 cycles of IVIG treatment (2 g/kg) without notable side effects. Since the first infusion of IVIG, the patient's skin lesions improved steadily and the improvement persisted until the 8-month follow-up. The eczema area and severity index score decreased remarkably, while immunologic parameters did not correlate with clinical improvement. This case suggests that IVIG therapy can be quite effective and safe for children with resistant AD.

IVIg therapy has potentially been related to arterial and venous therapy. We performed an Ovid review focusing on IVIg and thrombotic events. While a few case reports were reviewed case series and case control studies were particularly reviewed in relation to thrombotic events. Outcomes demonstrate a correlation between underlying cardiovascular risk factors with predominately arterial events which typically occurred within 4–24 hours of infusion. While venous events occurred less commonly they were associated with traditional risk factors and occurred later, typically, 1–7 days following infusion of IVIg. Potential causation of thrombotic events was discussed.

Intravenous Immunoglobulins (IVIg) are administered both as replacement therapy for certain immunodeficiencies and as immunomodulatory therapy for some autoimmune diseases. While the treatment with IVIg is approved in only a few autoimmune diseases, the number of off-label indications is increasing. The varied mechanisms by which IVIg attains its beneficial effect are diverse. There is much evidence for the beneficial and safety profile for IVIg in low as well as high-dose protocols. Patients prone to develop thrombotic events should be advised about the risk of IVIg therapy especially at high doses. This paper updates the mechanisms of action of IVIg as well as recent off-label indications.

Purpose A review of the different formulations of intravenous immunoglobulin (IVIG) replacement therapy for primary immunodeficiency and other severe diseases, focusing on the comparative efficacy, safety, and tolerability of these formulations. This review discusses the manufacturing processes, physicochemical properties, and other attributes of IVIG therapy that affect its clinical utility. Summary IVIG therapy is a preferred treatment for patients with certain types of primary immunodeficiency, neuroimmunologic, and autoimmune hematologic disorders, as well as for immunomodulation in bone marrow and some solid organ transplants. The IVIG products available in the United States include lyophilized, 5% liquid, and 10% ready-to-use liquid formulations. Differences among these formulations in their manufacturing processes, excipients, pH, and physicochemical properties may be reflected as differences in clinical efficacy, safety, and tolerability. For example, compared with lyophilized and 5% liquid IVIG formulations, 10% ready-to-use IVIG liquid formulations may be associated with better tolerability because of lower IgA concentrations, optimal pH, use of glycine or proline stabilizers, low sodium content, and less osmolality. Liquid formulations (both 5% and 10%) may provide greater convenience than lyophilized formulations for both patients and health care providers, because they do not require further dilution before administration and have shorter infusion times. Conclusion Before selecting an IVIG product for a hospital formulary, pharmacists should be knowledgeable about the product's concentration to ensure delivery of the proper dosage, the staff training needed for proper administration, the potential benefits and problems of brand substitution, the safety and efficacy of each formulation, the hospital's policies on off-label use of IVIG, and the impact of reimbursement.

Citation Winger EE, Reed JL, Ashoush S, El-Toukhy T, Ahuja S, Taranissi M. Elevated preconception CD56+16+ and/or Th1:Th2 levels predict benefit from IVIG therapy in subfertile women undergoing IVF. Am J Reprod Immunol 2011; 66: 394–403 Problem We sought to answer two questions: First, is there a group of patients who benefit from intravenous immunoglobulin (IVIG) in IVF? Second can this group of patients be identified by preconception blood testing? Method of study A total of 202 IVF cycles in subfertile women were divided into four groups. Group I: 62 cycles with preconception Th1:Th2 ratio and/or % CD56+ cell elevation using IVIG; Group II: 27 cycles with similar Th1:Th2 and/or % CD56+ cell elevation not using IVIG; Group III: 71 cycles with normal Th1:Th2 and/or % CD56+ cell levels using IVIG; Group IV: 42 cycles with normal Th1:Th2 and % CD56+ levels not using IVIG. These groups were similar with regard to patient age, diagnosis, and past failure history. Results The implantation rate (number of gestational sacs per embryo transferred, with an average of two embryos transferred per cycle) was 45% (55/123), 22% (12/54), 54% (75/139), and 48% (40/84) for Groups I–IV, respectively. The clinical pregnancy rate (fetal heart activity per IVF cycle started) was 61% (38/62), 26% (7/27), 69% (49/71), and 71% (30/42), respectively. The live birth rate was 58% (36/62), 22% (6/27), 61% (43/71), and 71% (30/42), respectively, and the live birth per embryo transferred was 40% (49/123), 13% (7/24), 43% (60/139), and 48% (40/84), respectively. There was a significant improvement in implantation, clinical pregnancy, live birth rate and live birth rate per embryo transferred for Group I versus Group II (P = 0.0032, 0.0021, 0.0017, and 0.0002, respectively) and for Group II versus Group IV (P = 0.0021, 0.0002