High-dose Gamma-globulin Therapy Research Articles

Clinical and imaging features of acute encephalopathy with biphasic seizures and late reduced diffusion in children

Objective: To explore the clinical and imaging features of acute encephalopathy with biphasic seizures and late reduced diffusion(AESD) in children. Methods: For the case series study, 21 children with AESD from Peking University First Hospital, Provincial Children's Hospital Affiliated to Anhui Medical University, Children's Hospital of Fudan University, and Shanxi Children's Hospital who were diagnosed and treated from October 2021 to July 2023 were selected. Clinical data were collected to summarize their clinical information, imaging, and laboratory tests, as well as treatment and prognostic characteristics. Descriptive statistical analysis was applicated. Results: Of the 21 cases with AESD, 11 were males and 10 were females, with the age of onset of 2 years and 6 months (1 year and 7 months, 3 years and 6 months). Of the 21 cases, 18 were typical cases with biphasic seizures. All typical cases had early seizures within 24 hours before or after fever onset. Among them, 16 cases had generalized seizures, 2 cases had focal seizures, and 7 cases reached the status epilepticus. Of the 21 cases, 3 atypical cases had late seizures in biphasic only. The late seizures in the 21 cases occurred on days 3 to 9. The types of late seizures included focal seizures in 12 cases, generalized seizures in 6 cases, and both focal and generalized seizures in 3 cases. Diffusion-weighted imaging (DWI) test on days 3 to 11 showed reduced diffusion of subcortical white matter which was named "bright tree sign" in all cases. The diffuse cerebral atrophy predominantly presented in the front-parietal-temporal lobes was found in 19 cases between day 12 and 3 months after the onset of the disease. Among 21 cases, 20 had been misdiagnosed as autoimmune encephalitis, central nervous system infection, febrile convulsions, posterior reversible encephalopathy syndrome, acute disseminated encephalomyelitis, and hemiconvulsion-hemiplegia-epilepsy syndrome. All the cases received high-dose gammaglobulin and methylprednisolone pulse therapy with poor therapeutic effect. By July 2023, 18 cases were under follow-up. Among them, 17 cases were left with varying degrees of neurologic sequelae, including 11 cases with post-encephalopathic epilepsy; 1 recovered completely. Conclusions: AESD is characterized by biphasic seizures clinically and "bright tree sign" on DWI images. Symptomatic and supportive treatments are recommended. The immunotherapy is ineffective. The prognosis of AESD is poor, with a high incidence of neurological sequelae and a low mortality.

頬部疼痛を契機に発見されたChurg-Strauss症候群の1例

Churg-Strauss syndrome is a rare, systemic inflammatory disease characterized by pre-existing type-I allergic symptoms, such as bronchial asthma or allergic rhinitis, and necrotic and granulomatous vasculitis with eosinophilia. We describe our experience with a case of this disease associated with cheek pain.A 64-year old man was referred to our hospital because of pain of the cheek and fever of unknown. He had a past history of chronic sinusitis. Computed fomography and magnetic resonance imaging showed bilateral multiple cystic lesions in the maxilla, and a postoperative maxillary cyst with infection was diagnosed initially.The patient received antibiotic therapy, but the symptoms did not improve. Blood examinations revealed eosinophilia and an increased serum IgE level. Symptoms of mononeuritis multiplex of the arm and leg, renal disorder, and micro-cerebral hemorrhage developed sequentially, and Churg-Strauss syndrome was given diagnosed. He received prednisolone and high-dose gamma globulin therapy, and the symptoms improved.

Clinical assessment of Mycoplasma pneumoniae‐associated hemophagocytic lymphohistiocytosis

Mycoplasma pneumoniae has been reported to be an etiologic pathogen of infection-associated hemophagocytic lymphohistiocytosis (HLH), but few case reports have been available to date. The clinical features of four childhood cases of M. pneumoniae-associated hemophagocytic lymphohistiocytosis (Mp-HLH) were retrospectively assessed to obtain data that might be useful for early diagnosis and effective management. The previous English-language literature pertaining to Mp-HLH was also reviewed. The patients were two boys and two girls, aged between 1 and 11 years of age. One patient was demonstrated to have concurrent infection with rubella. All the patients had typical radiographic features of M. pneumoniae pneumonia, and one patient also had encephalopathy as a complication. All the children underwent bone marrow examination because of antibiotic-refractory fever, mild hepatosplenomegaly, cytopenia, hyperferritinemia and elevated levels of urine beta2-microglobulin. Cytopenia and hepatosplenomegaly in the present patients were relatively mild as compared to those in cases of other infection-associated HLH such as Epstein-Barr virus infection-associated HLH. Treatment with corticosteroids resulted in prompt and complete resolution in two cases, and i.v. high-dose gammaglobulin therapy achieved a complete response in another child. Spontaneous resolution under treatment with antibiotics alone was observed in one case. Although Mp-HLH is a rare complication of M. pneumoniae infection, it should always be considered in patients with antibiotic-refractory M. pneumoniae infections with cytopenia. Mp-HLH might be effectively treated by corticosteroids or high-dose gammaglobulin. To clarify the diverse clinical manifestations of M. pneumoniae infections, immunological interactions between M. pneumoniae and the host immune system should be further investigated.

Successful Treatment of Neonatal Herpes Simplex-Type 1 Infection Complicated by Hemophagocytic Lymphohistiocytosis and Acute Liver Failure

Neonatal disseminated herpes simplex virus (HSV) infection with acute liver failure (ALF) and neonatal hemophagocytic lymphohistiocytosis (HLH) are severe diseases. We recently experienced a male infant with HLH and ALF induced by HSV type 1 (HSV-1). The infant, born at 39 weeks of gestation by normal delivery, developed a fever on day 4. On day 9, laboratory investigations showed progressive liver dysfunction and coagulopathy, and the serum ferritin was excessively elevated. Furthermore, the blood levels of interleukin (IL)-6, IL-10, and interferon-gamma were also elevated. HSV-1 DNA was detected in the serum and cerebrospinal fluid by the real-time PCR method. A diagnosis of HLH was established based upon the following criteria: fever, splenomegaly, cytopenia (two cell lines), serum ferritin (> 500 mug/l) and hypofibrinogenemia (< 150 mg/dl). High-dose acyclovir therapy, steroid pulse therapy using methylprednisolone, high-dose gamma globulin therapy and a blood transfusion were given. The patient recovered without neurological deficit. Neonatal disseminated HSV infections may be complicated by the development of HLH and hypercyokinemia. If HLH is suspected, not only high-dose acyclovir therapy but also anti-cytokine therapy should be considered.

Prediction of non-responsiveness to standard high-dose gamma-globulin therapy in patients with acute Kawasaki disease before starting initial treatment

Clinical, laboratory, and echocardiographic data were retrospectively analyzed in 112 patients with acute Kawasaki disease who received high-dose (2 g/kg) intravenous gamma-globulin (IVIG) treatment within 2 days and were compared for those who were responsive and non-responsive to initial IVIG treatment. Coronary arteries adjusted for body surface area (BSA) were evaluated quantitatively by comparison with the mean dimensions for 85 normal control subjects. The incidence of coronary abnormalities was higher in IVIG-non-responsive patients as compared to IVIG-responsive patients (71% versus 5%, p<0.0001). Univariate analysis of pre-IVIG data showed that the neutrophil count and serum levels of C-reactive protein (CRP), total bilirubin (TB), aspartate aminotransferase (AST), alanine aminotransferase, and lactate dehydrogenase (LDH) were significantly higher in IVIG-non-responsive versus responsive patients. Multivariate analysis selected CRP (p=0.009), TB (p<0.001), and AST (p=0.002) as independent predictors of non-responsiveness to initial IVIG treatment. By defining predictive values, patients with at least two of three predictors (CRP>or=7.0 mg, TB>or=0.9 mg, or AST>or=200 IU/L) are considered to be non-responsive to IVIG for acute Kawasaki disease. Alternatively, more intense initial therapy may be a promising therapeutic strategy for patients who are predicted to be IVIG-non-responsive.

特発性血小板減少性紫斑病患者の抜歯におけるγ‐グロブリン大量療法の検討

特発性血小板減少性紫斑病患者の抜歯におけるγ‐グロブリン大量療法の検討

Long-Term Changes in Coronary Artery Aneurysms in Patients With Kawasaki Disease-Comparison of Therapeutic Regimens-

There are few studies of the therapeutic regimens for the prevention of stenotic transformation of aneurysms in Kawasaki disease (KD). The aim of this study was to assess the prophylactic effect of combined therapy in the acute stage and convalescent- to chronic-stage against the formation of stenotic lesions. In 85 patients, 103 giant aneurysms (ANl), 46 medium-sized aneurysms (ANm), and 13 small aneurysms (ANs) were analyzed. With respect to therapy in the acute stage, no localized stenosis of ANl in the left coronary artery was noted in patients who received high-dose gamma globulin therapy (G). For ANm, the group (G) showed a significantly higher regression rate than the aspirin group and steroids group. Furthermore, no coronary artery occlusion/recanalization of ANl occurred with the prophylactic regimen of aspirin and warfarin {aw}. Prophylaxis {aw} and the prophylactic regimen of aspirin alone {a} significantly lowered the incidence compared with either the prophylactic regimen of warfarin {w} or no prophylaxis {n}. However, no significant differences were noted between prophylaxis {w} and {n}. High-dose gamma globulin therapy in the acute stage of KD is the first choice for the prevention of stenotic transformation. Prophylaxis {aw} is recommended for ANl.

Unusual antibody titer in a severe case of rhesus incompatibility

Unusual antibody titer in a severe case of rhesus incompatibility

血液疾患を合併した手術症例の検討

We reviewed 28 cases with serious blood dyscrasias who underwent orthopaedic surgery, and studied their perioperative management. 10 of the 28 cases were suffering from fractures. 5, 4, 3, and, 3 cases were suffering form tumors, lumber degenerative disorders, infection, and osteonecrosis of the femoral head, respectively. Acute leukemia was the major combined blood disease, which occurred in 9 cases. Idiopathic thrombocytopenic purpura (ITP) was found in 5 cases. We preoperatively gave platelet transfusions to the patients, if laboratory data showed their platelet counts were under 5×104/mm3. High-dose gammaglobulin therapy was an effective treatment for ITP. We managed to achieve platelet counts of over 5×104/mm3 in all patients. Leukocyte poor red cells were used for blood transfusion, if necessary, to avoid graft versus host disease. In all cases, the perioperative course was uneventful.

High-dose gammaglobulin (IVIG) followed by intrauterine transfusions (IUTs): a new alternative for the treatment of severe fetal hemolytic disease.

Intrauterine fetal transfusion is currently the therapy of choice in cases of severe anti-D isoimmunisation. However, its efficacy is reduced in patients with early severe hydrops fetalis due to the technical difficulties in performing this procedure before 20 weeks' gestation. The purpose of this study was to determine whether early onset of high-dose gammaglobulin therapy followed by intrauterine transfusions (IUTs) is more effective than IUTs alone in the treatment of very severe isoimmunised fetuses. The population studied in this retrospective clinical research was assigned to one of the following two groups: 1) Gamma group: 30 patients receiving gammaglobulin therapy before 21 weeks' gestation and IUTs after 20 weeks; or 2) IUT group: 39 patients receiving IUT treatment starting at a gestational age of 20-25 weeks. Both groups were statistically similar regarding history of perinatal deaths and anti-D antibody titers. The number of hydropic fetuses at the first IUT and of fetal deaths were significantly higher in the IUT than in the Gamma group. No significant differences were observed between the groups in fetal hematocrit at first IUT and at birth. However, the percentage of severely anemic fetuses was higher in the IUT group. Fetal mortality rate was 36% less in the Gamma group. Our results suggest that high-dose gammaglobulin therapy followed by IUTs may improve fetal survival in these severe cases. Further randomised clinical trials are needed to confirm these results.

Chronic childhood idiopathic thrombocytopenia purpura: long‐term follow‐up

An understanding of the natural history of childhood chronic idiopathic thrombocytopenia purpura (ITP) could contribute to a rational therapeutic approach to its treatment, which remains controversial. In our retrospective study of 92 children with ITP, 22 had a chronic course and were followed for 3-14 years (median 8.6 years). Treatment, when indicated, was individualized: 4 patients (18.2%) did not receive any treatment, 14 (63.6%) received steroids only, while 4 (18.2%) were treated with steroids and one of the following: high-dose gamma globulin (4 patients), splenectomy (2 patients) or immunosuppressive therapy (2 patients). During follow-up, 14 patients (63.6%) achieved complete remission, 5 (22.7%) partial remission and only 3 (13.5%) remained severely thrombocytopenic, with minimal bleeding tendency. Eleven patients (50%) responded to the initial prednisone course (1-5 mg/kg/day), but showed a marked decrease in platelet count when steroids were tapered off. In view of the high rates of complete and partial remission and the mild course of the few non-responding patients, it is suggested that with adequate supportive therapy, follow-up problems and fatalities can be kept to a minimum. We believe that aggressive therapy, such as splenectomy, should be reserved for the rare symptomatic and severely thrombocytopenic patient.

Successful anti‐D immunoglobulin therapy in refractory chronic idiopathic thrombocytopenic purpura showing reduction in thrombocytes even after splenectomy

An 8 year old female child was treated with steroid hormones, anabolic steroid hormones and high dose gamma-globulin therapy for 2 years since being diagnosed with idiopathic thrombocytopenic purpura at the age of 6 years. Treatment produced only transient efficacy, and thrombocytopenia persisted. A scintigram taken 2 years after the onset of the disease using [125I]-labelled heated auto red cells revealed accumulation of radioactivities in the spleen, and therefore splenectomy was performed. However, thrombocytopenia (10 x 10(9)/L) developed again 3 weeks after the operation, for which she was treated again with high dose gamma-globulin with only transient recovery. Then, anti-D immunoglobulin was injected intramuscularly at 250 micrograms per dose for a total of four doses and the platelet count was restored to the normal range. Since then her platelet count has been maintained higher than 200 x 10(9)/L for these 11 months. The scintigram taken after splenectomy showed an accumulation of radioactivities in the liver. After administration of anti-D immunoglobulin, transient subclinical hemolysis appeared. The mechanism whereby anti-D immunoglobulin exerts the efficacy described here may be considered to be by blockage of Fc receptors of macrophages, as is the case for high dose gamma-globulin therapy. However, since the recovery in the platelet count persisted, it appears that changes in the immune system other than the above described mechanism have contributed to the recovery.

The Cases of Tooth Extraction under High-dose Gamma-globulin Therapy in Patients, Diagnosed as Chronic Idiopathic Thrombocytopenic Purpura with Antiplatelet Antibodies

The Cases of Tooth Extraction under High-dose Gamma-globulin Therapy in Patients, Diagnosed as Chronic Idiopathic Thrombocytopenic Purpura with Antiplatelet Antibodies

T, B cell surface marker in Kawasaki disease and effect of high-dose gamma globulin therapy for high-risk children

T, B cell surface marker in Kawasaki disease and effect of high-dose gamma globulin therapy for high-risk children

The Onset of Coronary Artery Aneurysm and Changes of T Cell Subsets and the Effect of High Dose Gammaglobulin Therapy in Mucocutanenous Lymph Node Syndrome

The Onset of Coronary Artery Aneurysm and Changes of T Cell Subsets and the Effect of High Dose Gammaglobulin Therapy in Mucocutanenous Lymph Node Syndrome

Inhibitory Effects of High Doses of Intravenous γ‐Globulin on Platelet Interaction with the Vessel Wall in Kawasaki Disease

Clinical effects of high-dose gamma-globulin therapy in Kawasaki disease have been evaluated from the viewpoints of its inhibitory effects on platelet adhesion and thrombus formation on the vessel wall. Platelet adhesion to the subendothelium is the fist step of thrombosis as well as platelet interaction with the vessel wall, which can be observed experimentally by Baumgartner's method. Twelve patients with Kawasaki disease treated with intact intravenous gamma-globulin (IVGG) showed decreased platelet adhesion in contrast to ten patients treated with only aspirin (ASA) or flurbiprofen (FP). Addition of intact IVGG to normal blood in Baumgartner's method also resulted in decreasing platelet adhesion and thrombus formation; however, other pepsin-treated IVGG caused enhanced platelet adhesion and thrombus formation. Moreover, pretreatments of the vessel wall with both types of IVGG showed effects similar to those of addition. In conclusion, high-dose therapy with intact IVGG has inhibitory effects on platelet adhesion and thrombus formation. Although the mechanism of the effects is not yet clear, some competitive inhibition between intact IgG and adhesive protein such as von Willebrand factor is suggested, and Fc receptors of the platelet membrane and Fab and Fc receptors of the subendothelium of the vessel wall may have some role in the interaction.

A B Cell line from a patient with pure red cell aplasia produces an immunoglobulin that suppresses erythropoiesis

A 4-year-old boy with pure red cell aplasia was investigated. Immunophenotypic analysis of peripheral blood lymphocytes revealed a marked increase of CD20+ cells, which fell from 25.9% in the active stage to 9.7% in remission. The plasma contained a suppressive activity against CFU-e and BFU-e formation by the patient's bone marrow cells, which disappeared when the disease went into remission. Prednisone (2 mg/kg/day) therapy was tried for 5 weeks, but produced no improvement. Subsequently, high-dose gamma-globulin therapy induced complete remission of anemia. A lymphoblastoid B cell line obtained from the patient before therapy produced a factor that suppressed erythropoiesis but not granulopoiesis. The suppressive activity resided in the immunoglobulin fraction and was adsorbed by an anti-immunoglobulin column. These results indicate that expansion of B cells producing an immunoglobulin which suppressed erythropoiesis was involved in the pathogenesis of the disease in this patient.

Aortic valve replacement and splenectomy in a patient with chronic idiopathic thrombocytopenic purpura—preoperative management with high-dose γ-globulin

We report the management of a patient with chronic idiopathic thrombocytopenic purpura and severe aortic valvular disease. Preoperative intravenous high-dose gamma-globulin administration was employed, and aortic valve replacement combined with splenectomy were performed during the same operation. The platelet count at admission was 34,000/mm3 and increased to 146,000/mm3 after the gamma-globulin therapy. Platelet transfusion at the end of the cardiopulmonary bypass was considered no longer necessary in the postoperative period, because the platelet count increased quickly after the procedure. The postoperative course was uneventful. We believe that open heart surgery and splenectomy can successfully be performed simultaneously in a patient with chronic idiopathic thrombocytopenic purpura treated with high-dose gamma-globulin therapy.

Ruptured Cerebral Aneurysm Successfully Clipped in Idiopathic Thrombocytopenic Purpura After High-dose Gamma-globulin Therapy

A ruptured cerebral aneurysm in a 50-year-old female with idiopathic thrombocytopenic purpura was successfully clipped after preoperative high-dose gamma-globulin therapy to control the hemorrhagic diathesis. High-dose gamma-globulin therapy with or without steroid and/or platelet transfusion is recommended for such cases if the blood pressure can be controlled and the neurological condition permits delayed surgery.

B‐Cell Function in Kawasaki Disease and the Effect of High‐Dose Gamma‐Globulin Therapy

We studied in vitro B-cell function in Kawasaki disease (KD). By plaque-forming assay, IgG-, IgA- and IgM-secreting cells in the first week of KD were markedly increased, and recovered to a normal level in the second week in many cases. Lymphocyte blast formation with Staphylococcus aureus Cowan I (SAC), a B-cell-specific mitogen, was suppressed in the acute phase, and recovered to a normal level in the convalescent phase. By flow cytometry, HLA-DR- and HLA-DQ-positive cells were increased in the acute phase of KD. CD3- and CD4-positive cells were also decreased. CD8-positive cells showed no significant change. In five patients, CD4-positive cells with HLA-DR positivity neither increased in the acute phase nor changed during the course of illness. From our results, it can be considered that pathogenic microorganisms or toxins activate B cells directly in KD without the association of T cells. We also studied the effect of high-dose gamma-globulin therapy on B-cell function in KD. However, the results indicated that this form of therapy had no significant effect on B-cell functions.