Intravenous Γ-globulin Research Articles

Clinical characteristics and antimicrobial resistance of pneumococcal isolates of pediatric invasive pneumococcal disease in China.

PurposeStreptococcus pneumoniae causes serious infections globally, including invasive pneumococcal disease (IPD). We analyze clinical features of pediatric IPD cases identified in China and antibiotic susceptibility of isolated pneumococcal strains.MethodsConfirmed pediatric IPD patients were prospectively recruited to the study. Symptoms at the time of hospitalization, laboratory tests, antimicrobial susceptibility of pneumococcal isolates, treatments, hospital stay, and residual findings at discharge were analyzed systematically.ResultsFrom January 2008 to December 2017, a total of 123 hospitalized children diagnosed with IPD were enrolled: 68 from pediatric departments of Xinhua Hospital, and 55 from Lanzhou University Second Hospital. Of these pediatric IPD patients, 81 (65.86%) were male, and 98 (79.67%) <5 years old. Most cases (96, 78.05%) were diagnosed during the cold season between September and February. Sepsis was observed in 82 (66.67%) patients, 48 (39.02%) children were diagnosed with meningitis, 41 (33.33%) with pneumonia, 30 (24.39%) with pleurisy, and 4 (3.25%) with osteomyelitis. Underlying diseases were noted in 35 (28.45%) patients and concurrent infections in 45 (36.58%). The overall mortality rate was 2.44%. IPD children who developed sepsis and necrotizing pneumonia showed higher proportions of intensive care-unit admission, intravenous γ-globulin, glucocorticoid use, hemofiltration and ventilator, and longer duration of fever, hospital stay, and antibiotic use than nonsepsis and pneumonia subjects. Antimicrobial resistance of S. pneumoniae showed a highly unsusceptible rate for erythromycin (96.75%), trimethoprim-sulfamethoxazole (79.67%), and tetracycline (77.23%). All isolates were sensitive to vancomycin, linezolid, and levofloxacin.ConclusionClinical symptoms were severe in the majority of pediatric IPD patients. More intensive treatments were demanded for IPD children with sepsis and necrotizing pneumonia. High resistance rates for erythromycin, trimethoprim–sulfamethoxazole, and tetracycline were found.

Hypoxemia is an independent predictor of bronchiolitis obliterans following respiratory adenoviral infection in children.

Bronchiolitis obliterans (BO) is an uncommon and severe sequela of chronic obstructive lung disease in children that results from an insult to the lower respiratory tract. Few prognostic factors achieved worldwide acknowledgment. In the present study, we retrospectively collected the children with respiratory adenoviral infection and identified the predictive factors of BO. In the period between Jan 2011 and December 2014, the consecutive in-hospital acute respiratory infection children with positive result for adenovirus were enrolled into the present study. High resolution computerized tomography and clinical symptoms were utilized as the diagnostic technique for BO. Multivariate analysis using a Logistic proportional hazards model was used to test for independent predictors of BO. A total of 544 children were included with 14 (2.57 %) patients developed BO. Compared with children without BO, BO children presented higher LDH (523.5 vs. 348 IU/ml, p = 0.033), lower blood lymphocyte count (2.23 × 109/L vs. 3.24 × 109/L, p = 0.025) and higher incidence of hypoxemia (78.6 vs. 20.8 %, p = 0.000). They presented relatively persistent fever (15.5 vs. 7 days, p = 0.000) and needed longer treatment in hospital (19.5 vs. 7 days, p = 0.000). Concerning treatment, they were given more intravenous γ-globulin (85.7 vs. 36.8 %, p = 0.000), glucocorticoids (78.6 vs. 24.3 %, p = 0.000) and mechanical ventilation (35.7 vs. 5.5 %, p = 0.001). Multiple analyses determined that hypoxemia was the only independent predictor for BO. The present study identified hypoxemia as the independent predictive factor of BO in adenoviral infected children, which was a novel and sensitive predictor for BO.

Abstract 108: New Assessment Of Comprehensive Coagulation Function Using Clot Waveform Analysis In Patients With Kawasaki Disease In The Acute Phase

Background: Hypercoagulability for Kawasaki disease (KD) in the acute phase is known, through many reports based on the change of the individual coagulation factor. Little information on the assessment of comprehensive coagulation function of this disease is described, however. A recent developed clot waveform analysis (CWA), defines changes in light transmittance that occur during the process of clot formation, can assess comprehensive coagulation function qualitatively and quantitatively by measuring the parameters. In this study, we have investigated the clotting dynamics of acute-phase KD by CWA. Method: The subjects were 43 patients of KD with treatment of intravenous γ-globulin (IVIG), at onset ranged from 3 months to 5 years old (median 1.8 years old). Normal pooled plasma (NP) was prepared from 20 healthy individuals. Blood samples were collected at three points of time; before the IVIG administration (Pre), after 1 week of IVIG (1W), and after 1 month of IVIG (1M). Cases with anticoagulant medication were excluded. CWA was performed using MDA-II™, and parameters, clotting time (CT), maximum coagulation velocity (dT/dt,

Peripartum Cardiomyopathy

Peripartum Cardiomyopathy

Treatment of Hemophagocytic Lymphohistiocytosis With Alemtuzumab in Systemic Lupus Erythematosus

Hemophagocytic lymphohistiocytosis (HLH) is an immune disorder characterized by cytokine dysregulation and uncontrolled activation of T lymphocytes and macrophages. It is categorized as primary when associated with specific genetic mutations or secondary when associated with infections, malignancies, or autoimmune disorders. Clinical features of HLH include unexplained fever, hepatosplenomegaly, pancytopenia, and severe hyperferritinemia. Treatment of primary HLH has become standardized based on the HLH-2004 protocol using cyclosporine, etoposide, and dexamethasone with or without intrathecal methotrexate followed by hematopoietic stem cell transplantation. Treatment of secondary HLH is directed at control of the underlying condition. If unsuccessful, cytotoxic agents such as those in HLH-2004, steroids, intravenous γ-globulin, or targeted immune therapy have been used. Immunotherapy targeting CD52 expressed on immune effector cells of HLH is a rational therapeutic approach in patients too ill for traditional cytotoxic chemotherapy. We describe the successful use of alemtuzumab to treat HLH due to systemic lupus erythematosus.

Pediatric Systemic Lupus Erythematosus: More Than a Positive Antinuclear Antibody

Based on strong research evidence and consensus, the most common disease manifestations at diagnosis of pSLE are constitutional symptoms, arthritis, and malar rash. Based on some research evidence and consensus, patients with pSLE tend to have major organ system involvement (renal/central nervous system) and a greater disease burden compared with adults. Despite these findings, mortality is low. Based on some research evidence and consensus, the diagnosis of pSLE is unlikely if the ANA is negative, and most patients with SLE have a positive ANA at a titer ≥1:160. Based on strong research evidence, both MMF and cyclophosphamide can be used for induction therapy in class III and IV lupus nephritis. Based on strong research evidence, patients with SLE and anticardiolipin antibodies or LA have a two and six times greater risk of venous thrombosis, respectively, compared with patients with SLE without antiphospholipid antibodies. Based on strong research evidence, patients with pSLE have a higher risk for subclinical atherosclerosis when there is weight-adjusted prednisone use, azathioprine use, increasing age, male gender, high BMI, abnormal creatinine clearance, and elevated lipoprotein(a) levels.

Hemophagocytic syndrome after liver transplantation: Report of two cases

We report two cases of hemophagocytic syndrome (HPS), a rare but fatal complication after living-donor liver transplantation (LDLT). Despite their recovery from pancytopenia following treatment with steroid pulse therapy, granulocyte stimulating factor, and intravenous γ-globulin, both patients died. The outcomes reported in cases published in English are devastating, with only 4 survivors among the total 14 patients including ours. Pancytopenia is frequently recognized postoperatively in liver transplant recipients, although its cause is difficult to establish. When pancytopenia accompanying persistent high fever is recognized in LDLT recipients, HPS should be suspected and bone marrow aspiration performed as promptly as possible because of the poor prognosis of this syndrome. There is still no optimal treatment for HPS after liver transplantation.

Coronary Involvement in Infants with Kawasaki Disease Treated with Intravenous γ-Globulin

To analyze the clinical spectrum and the incidence of coronary involvement in infants with typical Kawasaki's disease (KD). A retrospective study was performed on children one year of age or younger diagnosed from February 1992 to January 2006 with typical KD. Children with incomplete forms of the disease were not included. Twenty-five infants were diagnosed with KD during the study period. The median age of the patients was 10 months (range, 4-12 months). All children but one received intravenous gammaglobulin (IVIG), 84% before the 10th day of disease. Seven patients (28%) required the administration of more than one dose of IVIG, because persistence of fever. Coronary artery disease (CAD) was recorded in 6 cases (24%), five of them being boys. All patients with CAD were treated with ASA plus IVIG and 84% of them received this therapy within the first 10 days of the KD onset. In spite of the exclusion of our study of incomplete presentations and of an early administration of IVIG in our patients, we have observed a high rate of infants who developed CAD, which is similar to the one reported in children who do not receive IVIG.

Progressive ataxic gait disorder

Paraneoplastic cerebellar degeneration (PCD) is a well-described paraneoplastic syndrome. In patients with anti-Yo associated PCD, neurological symptoms precede the diagnosis of the underlying cancer in approximately 60% of cases. Ovarian, breast and other gynaecological malignancies are most frequently found as causative malignancies. Antitumour treatment should be commenced at an early stage of the disease. Identification of the tumour is a diagnostic challenge in many of these patients. In the case reported herein, a secondary tumour with unknown primary was suggested after detection of a pathological lymph node in the right axilla by a positron emission tomography scan. Microscopic examination of the ultrasound-guided resected tissue was a poorly differentiated adenocarcinoma strongly positive for the C-ERB 2 oncoprotein. A micro-invasive mammary carcinoma was unable to be localized, even with the aid of magnetic resonance mammography and axillary clearance. Intravenous γ-globulin and steroid treatment and rehabilitation failed to influence the neurological symptoms. The present patient also demonstrated diffuse increase on the T 2 signal in the cerebellum, which may provide a useful diagnostic clue in the assessment of PCD.

Pathology and protection in nephrotoxic nephritis is determined by selective engagement of specific Fc receptors

Introduction of heterologous anti–glomerular basement membrane antiserum (nephrotoxic serum, NTS) into presensitized mice triggers the production of IgG anti-NTS antibodies that are predominantly IgG2b and the glomerular deposition of pathogenic immune complexes, leading to accelerated renal disease. The pathology observed in this model is determined by the effector cell activation threshold that is established by the coexpression on infiltrating macrophages of the IgG2a/2b restricted activation receptor FcγRIV and its inhibitory receptor counterpart, FcγRIIB. Blocking FcγRIV with a specific monoclonal antibody thereby preventing IgG2b engagement or treatment with high dose intravenous γ-globulin (IVIG) to down-regulate FcγRIV while up-regulating FcγRIIB, protects mice from fatal disease. In the absence of FcγRIIB, IVIG is not protective; this indicates that reduced FcγRIV expression alone is insufficient to protect animals from pathogenic IgG2b immune complexes. These results establish the significance of specific IgG subclasses and their cognate FcγRs in renal disease.

Initial Intravenous γ-Globulin Treatment Failure in Iranian Children with Kawasaki Disease

The purpose of this study was to determine the initial rates of intravenous gamma-globulin treatment (IVIG) failure in Kawasaki disease (KD) and their predisposing factors. This study was a retrospective analysis of the initial response to IVIG (2 g/kg), assessed from the medical reports of all patients admitted to Namazee Hospital pediatric ward, from March 1998 to March 2002, and who fulfilled the criteria for KD. Data were available for 64 patients, 58 of whom (90.6%) became afebrile 48 hours after completion of the initial dose of IVIG (Group I) and six (9.4%) who remained febrile (Group II). Two patients had a prompt response to a second dose of IVIG. In Group I, five patients (8.6%) developed coronary artery disease, seen on echocardiography. In Group II, two patients (33.3%) developed coronary artery disease. No significant difference was found in the prevalence of coronary artery disease between the two groups (p = 0.12), or in age or gender. The rate of initial treatment failure was 9.4% in this cohort of patients, which is comparable with previous reports. No predictive factors such as coronary artery disease, age or gender were found for initial treatment failure in KD.

Respiratory syncytial virus infection in elderly adults.

Respiratory syncytial virus (RSV) infection is now recognised as a significant problem in elderly adults. Epidemiological evidence indicates the impact of RSV in older adults may be similar to nonpandemic influenza, both in the community and in long-term care facilities. Attack rates in nursing homes are approximately 5–10% per year with significant rates of pneumonia (10–20%) and death (2–5%). Estimates using US healthcare databases and viral surveillance results over a 9-year period indicate that RSV infection causes approximately 10 000 all-cause deaths annually among persons >64 years of age. In contrast, influenza A accounted for approximately 37 000 yearly deaths in the same age group. The clinical features of RSV infection may be difficult to distinguish from those of influenza but include nasal congestion, cough, wheezing and low-grade fever. Older persons with underlying heart and lung disease and immunocompromised patients are at highest risk for RSV infection-related pneumonia and death. Diagnosis of RSV infection in adults is difficult because viral culture and antigen detection are insensitive, presumably because of low viral titres. The combination of serology and reverse transcriptase polymerase chain reaction assay offers the best sensitivity and specificity for the diagnosis of RSV but unfortunately these techniques are not widely available; consequently, most adult RSV disease goes unrecognised. Although treatment of RSV infection in the elderly is largely supportive, early therapy with ribavirin and intravenous γ-globulin improves survival in immunocompromised persons. An effective RSV vaccine has not yet been developed. Therefore, prevention of RSV is limited to standard infection control practices, such as hand washing and the use of gowns and gloves.

Hypercytokinemia is Not Originated from Peripheral Mononuclear Cells at Acute Phase of Kawasaki Disease

Immune activation and generalized vasculitis are two central features of Kawasaki disease (KD). Recent observations indicated that serum levels of cytokines including interferon(INF)- γ, tumor necrosis factor (TNF)- α and interleukin (IL)-1 are remarkably increased, and that the administration of intravenous γ-globulin (IVGG) reduces the levels of elevated cytokines. Objective: We examined whether the plasma exchange (PE) for intractable KD cases reduces the elevated serum cytokines, and whether hypercytokinemia is originated from peripheral mononuclear cells at acute phase. Materials and Methods: We first compared the serum levels of cytokines between pre- and post-treatment of IVGG (8 cases) and PE (8 cases), using ELISA and cytometric bead array (CBA) system (Becton & Dickinson). For 4 cases among them, we investigated the messenger RNA levels of several cytokines in peripheral mononuclear cells at acute phase, using ribonuclease protection assay (RPA) system (Becton & Dickinson). Results: In sera of the children intractable to IVGG, increased levels of cytokines were detected such as INF-γ, IL-6, IL-10 and soluble TNF receptor (sTNFR). After PE therapy, serum levels of them markedly decreased to the normal ranges (INF-γ: 9.1 ± 13.4 →4.0 ± 6.4 pg/ml, IL-6: 67.5 ± 74.3→6.6 ± 8.4 pg/ml, IL-10: 14.1 ± 5.1→7.4 ± 2.1 pg/ml, sTNFR: 2521.9 ± 728.2→1338.2 ± 575.9 pg/ml). However, RPA analysis demonstrated that messenger RNA levels of several cytokines at acute phase were undetectable in both pre- and post-treatment of PE in peripheral mononuclear cells. Discussion: These findings suggested that the effectiveness of IVGG and PE treatment for KD will be attributed to the reduction of proinflammatory cytokine levels in serum, and that the increased levels of proinflammatory cytokines were originated not from the circulating mononuclear cells, but presumably from in situ lymphocytes and macrophages located at inflammatory lesion such as vasculitis lesion.

γ-Globulins prepared from sera of multiparous women bind anti-HLA antibodies and inhibit an established in vivo human alloimmune response

AbstractIt has previously been shown that sera from multiparous women have increased levels of anti-idiotypic antibodies specific for anti-HLA molecules. γ-Globulins prepared from these sera may be superior to commercial preparations of intravenous γ-globulin (IVIg) for inhibiting HLA alloimmunization. To test this, F(ab′)2fragments prepared from either commercial IVIg or from the sera of men or multiparous women were coupled to CNBr-Sepharose and tested for their ability to bind F(ab′)2 fragments derived from polyspecific anti-HLA sera. As determined by flow cytometry, compared with columns coated with F(ab′)2 derived from commercial IVIg or sera from men, columns coated with F(ab′)2 prepared from the sera of multiparous women bound significantly more anti-HLA. In addition, intact IgG molecules prepared from the sera of multiparous women significantly neutralized the reactivity of the anti-HLA F(ab′)2 fragments. To determine whether the intact IgG molecules or their corresponding F(ab′)2 fragments could affect in vivo alloimmunity, they were tested for their ability to inhibit an established IgG human alloimmune response in humanized severe combined immunodeficient (SCID) mice. Compared with commercial IVIg, when intact IgG or F(ab′)2 fragments derived from multiparous women were administered to SCID mice making human anti-HLA antibodies, a significant reduction in anti-HLA reactivity was observed. The findings suggest that IgG molecules prepared from the sera of multiparous women have increased anti-idiotypic reactivity against anti-HLA antibodies, which can significantly inhibit an established human IgG alloimmune response in an Fc-independent manner.

Long-Term Follow-Up with Stress Echocardiograms of Patients with Kawasaki’s Disease

Patients with a history of Kawasaki’s disease (KD), particularly those not treated with intravenous γ-globulin, are at risk of coronary artery aneurysms and later obstruction. Twenty-eight patients with a history of KD (4 had coronary artery aneurysms) were examined with stress echocardiograms. Fourteen patients received γ-globulin ≤10 days of the onset, 8 patients received γ-globulin >10 days and 6 received no γ-globulin. The mean age at diagnosis was 7.2 ± 4.1 years; the median follow-up was 8.0 ± 7.4 years. All tests were negative. Using a binomial model, a power of 0.80, a sensitivity of each test of 80% and assuming uniform risk, the individual rate of failure to detect was <7%. At least 640 patients in each group would be needed to detect a difference of 3.5% vs. 7.0% and 184 in each group would be needed to detect a difference of 1.5% vs. 7.5%. We conclude that the probability of an abnormal stress echo in asymptomatic patients with a history of KD is at most 7% and that a more precise determination of the risk of an abnormal stress echo in KD requires a much larger study.

Immune thrombocytopenic purpura associated with rheumatoid arthritis - a report of five cases and review of the literature

Immune thrombocytopenic purpura (ITP) associated with rheumatoid arthritis (RA) is relatively rare. We describe five cases of RA with ITP. In all five patients, platelet counts were low, platelet-associated IgG levels were elevated, and bone marrow aspiration showed megakaryocytosis. Glucocorticoid therapy was effective in three cases, but the other two cases required immunosuppressants or intravenous γ-globulin in addition to glucocorticoid. We review the reported cases of RA with ITP and discuss the pathophysiology and differential diagnosis of thrombocytopenia in RA.

Four-Year Experience with Serious Adverse Reactions to Intravenous γ-Globulin at a Tertiary Medical Center

Reports of the true incidence of adverse reactions to intravenous γ-globulin (IVIG) therapy are limited by the lack of studies documenting reactions in a large number of patients. The objective was to describe the frequency of serious side effects to intravenous immune globulin therapy at a major tertiary medical center between 1991 and 1995. A central pharmacy registry of a tertiary medical center was searched for all patients and doses of intravenous immune globulin therapy given in both the inpatient and outpatient setting. Records of patients were reviewed for specific details regarding an adverse reaction. Acute renal failure occurred in 2 of 194 (1%) patients and aseptic meningitis occurred in 4 of 194 (2%) patients. Renal failure occurred in 2 of 1637 (0.1%) of infusions and aseptic meningitis occurred in 5 of 1637 (0.3%) of infusions. Both cases of renal failure were adults receiving high doses (2 g/kg) of IVIG. Of the 4 patients who developed aseptic meningitis, 3 were adults and 1 was a child. Aseptic meningitis occurred in 3 patients receiving high dose and 1 patient receiving low dose (400 mg/kg) IVIG therapy. Acute renal failure and aseptic meningitis are rare side effects of IVIG therapy. Renal failure occurred only in adults with high-dose therapy. Possible risk factors for developing this complication include preexisting renal insufficiency, diabetes, older age, and concomitant diuretic use. Unlike previous studies, we found that aseptic meningitis can occur after administration with low doses of IVIG. (Pediatr Asthma Allergy Immunol 2000;14[4]:287-292.)

Pediatric Clostridium difficile: a phantom menace or clinical reality?

Clostridium difficile is the leading cause of nosocomial gastrointestinal illness in adult patients in hospitals. Even though C. difficile disease in adults has been well studied, research on pediatric C. difficile disease is still in its infancy. For many years it has been believed that C. difficile was a disease that affected only adults and was not a problem for children. This erroneous belief arose from the observation that neonates acquire C. difficile quickly (within 48 hours of birth) but show no intestinal symptoms (1–4). More recent evidence has been documented in case reports of pediatric C. difficile and outbreaks of C. difficile disease in pediatric populations (5– 7). Pediatric C. difficile disease has also been associated with the occurrence of severe complications and high mortality rates (8–10). The cascade of events in the pathogenesis of C. difficile disease is similar in children and adults. Normal intestinal microflora are disrupted by antibiotic exposure, medications, or surgery. If the child is then exposed to C. difficile (or its spores), colonization may occur, with production of toxins A and B. These toxins act on enterocytes, causing an inflammatory response and morphologic changes that lead to diarrhea or colitis. Host factors (age, diet, immune response) play an important role in determining whether C. difficile develops into asymptomatic carriage or active disease. Treatment for pediatric C. difficile disease usually relies on metronidazole or vancomycin, but clinical guidelines have not been defined for the pediatric population (11). As in adults, recurrent C. difficile disease that does not respond to conventional therapy develops in a proportion of children treated with antibiotic therapy.

Predictors of coronary artery lesions after intravenous γ-globulin treatment in Kawasaki disease

Objective: We evaluated the efficacy of intravenous γ-globulin (IVGG) administration for children with Kawasaki disease to establish whether additional, more advanced therapy is needed in intractable cases. Study design: A total of 193 children with Kawasaki disease were studied retrospectively. Patients were admitted 3 to 7 days after the onset of the disease, and IVGG was administered. Laboratory measurements including white blood cell (WBC), neutrophil, and platelet counts and C-reactive protein (CRP) and albumin concentrations were determined before and 2 to 3 days after IVGG treatment. The progression of coronary artery lesions (CALs) was monitored by serial echocardiography until 30 days after treatment. Results: Of 193 children, 24 (12.2 %) had CALs including transient dilatation. In contrast to the other measurements, the WBC count increased in 21 of 24 (87.5%) children with CALs after IVGG therapy. The patients with increased neutrophil count and CRP concentration after IVGG therapy also had CAL formation at a high rate (78.3% and 66.7%, respectively). Among children with normal coronary arteries, elevations of the WBC and neutrophil counts and CRP concentration were observed after IVGG therapy in only 3, 6, and 8 patients, respectively (specificity: 98.2%, 97.0%, and 95.3%, respectively). Furthermore, multiple logistic regression indicated that these variables were useful predictors of CALs in KD. Conclusion: Though the introduction of IVGG therapy has improved the prognosis of Kawasaki disease, approximately 10% of patients still develop CALs. The need for more aggressive therapy in IVGG-resistant cases can be recognized early by increases in the WBC and neutrophil counts and serum CRP concentration after IVGG administration. (J Pediatr 2000;137:177-80)

Redo without transfusion in a patient with idiopathic thrombocytopenic purpura

Mitral valve replacement was able to be carried out at redo operation requiring neither allogeneic platelet nor blood transfusion in a patient with idiopathic thrombocytopenic purpura, by means of preoperative high-dose intravenous γ-globulin, autologous blood predonation, use of a centrifugal pump, heparin-coated extracorporeal circuits, and simultaneous splenectomy.