High-dose Intravenous Gammaglobulin Research Articles

A Case of Thrombocytopenia with <italic>MYH9</italic> Gene Mutation Found in Siblings

Myosin heavy chain 9 (MYH9) related diseases are autosomal dominant diseases characterized by macrothrombocytopenia and inclusion bodies in leukocyte, which can be accompanied by extra-hematologic symptoms such as sensorineural hearing loss, renal dysfunction, and cataract. They are often diagnosed incidentally in adulthood or misdiagnosed as idiopathic thrombocytopenic purpura (ITP), leading to unnecessary treatment with intravenous high-dose gamma-globulin, steroids, or splenectomy. Here, we report the case of a brother and sister confirmed to have a MYH9 gene mutation during follow-up. An 8-year-old boy was confirmed to have thrombocytopenia at birth and treated with intravenous gamma-globulin under suspicion of ITP or sepsis. He was discharged after showing an increase in platelet count. Subsequently, during outpatient workup, he exhibited thrombocytopenia, large platelets, and neutrophilic inclusion bodies. His 10-year-old sister also presented with the same findings. In 2021, DNA analysis revealed that they share a mutation (c.4270G> A, p. Asp1424Asn), a pathogenic variant associated with MYH9-related disorder.

A case of bullous pemphigoid following administration of anti-IL-31 receptor A antibody.

Bullous pemphigoid (BP), an autoimmune bullous dermatosis, occurs predominantly in older individuals. Nemolizumab, a humanized monoclonal antibody against the interleukin (IL)-31 receptor A, is used to treat severe atopic dermatitis (AD) in Japan. However, it can cause several adverse events, such as exacerbation of AD, erythema, and eosinophilia. Herein, we describe a case of prurigo-type AD developing BP after nemolizumab administration. A 62-year-old man with prurigo-type AD and asthma presented with serious, refractory itching. After nemolizumab injection, his pruritus was relieved for 2 days. However, on day 3, erythema with blisters and erosions suddenly appeared throughout his body. Pathological examination showed typical BP and the patient's serum anti-BP180-NC16a antibody level was 882.5 U/mL. Oral prednisolone (PSL) was initiated and nemolizumab was never used again. Despite high-dose PSL, new blisters continued to develop, with a rapid elevation of anti-BP180-NC16a antibodies to 6930 U/mL. Adding high-dose cyclosporine and intravenous gamma globulin reduced new blister formation after 9 weeks, and PSL and cyclosporine were gradually tapered. Dupilumab, an anti-IL-4 receptor antibody, was initiated after 16 weeks, resulting in continued remission without PSL and cyclosporine. The sudden occurrence of BP in this case suggested that the patient had occult BP before the nemolizumab initiation and that nemolizumab exacerbated BP and made it overt. Blocking the IL-31 pathway may exacerbate inflammation in AD or BP, resulting in the acceleration of blister formation. This may be countered by blocking the IL-4/13 pathway with dupilumab. To our knowledge, this is the first case of nemolizumab-exacerbated BP.

Pharmacogenomics of intravenous immunoglobulin response in Kawasaki disease.

Kawasaki disease (KD) is a diffuse vasculitis in children. Response to high dose intravenous gamma globulin (IVIG), the primary treatment, varies according to genetic background. We sought to identify genetic loci, which associate with treatment response using whole genome sequencing (WGS). We performed WGS in 472 KD patients with 305 IVIG responders and 167 non-responders defined by AHA clinical criteria. We conducted logistic regression models to test additive genetic effect in the entire cohort and in four subgroups defined by ancestry information markers (Whites, African Americans, Asians, and Hispanics). We performed functional mapping and annotation using FUMA to examine genetic variants that are potentially involved IVIG non-response. Further, we conducted SNP-set [Sequence] Kernel Association Test (SKAT) for all rare and common variants. Of the 43,288,336 SNPs (23,660,970 in intergenic regions, 16,764,594 in introns and 556,814 in the exons) identified, the top ten hits associated with IVIG non-response were in FANK1, MAP2K3:KCNJ12, CA10, FRG1DP, CWH43 regions. When analyzed separately in ancestry-based racial subgroups, SNPs in several novel genes were associated. A total of 23 possible causal genes were pinpointed by positional and chromatin mapping. SKAT analysis demonstrated association in the entire MANIA2, EDN1, SFMBT2, and PPP2R5E genes and segments of CSMD2, LINC01317, HIVEPI, HSP90AB1, and TTLL11 genes. This WGS study identified multiple predominantly novel understudied genes associated with IVIG response. These data can serve to inform regarding pathogenesis of KD, as well as lay ground work for developing treatment response predictors.

The Improvement Effect of Different Doses of Gamma Globulin on the Disease Condition of Infants with Hemolytic Disease of Newborn and Their Effects on Immune Factors in Serum

To explore the effect of different doses of Gamma Globulin (GG) on the condition of children with Hemolytic Disease of Newborn (HDN) and the influence of immune factors in serum. Overall, 180 infants with hemolytic disease of newborn in the People's Hospital of Zhangqiu Area, Jinan, China from April 2016 to August 2018 were divided into group A (88 cases) and group B (92 cases). Group A was given intravenous low-dose GG on the basis of phototherapy, and group B was given intravenous high-dose GG on the basis of phototherapy. The level of serum total bilirubin of the infants, the levels of CD3+, CD4+, CD8+, IgA, IgG and IgM of the infants, the time of jaundice disappearance and the length of hospital stay, hemoglobin and reticulocyte levels were recorded before treatment and after treatment. The number and condition of adverse reactions were recorded. After treatment, the levels of TBiL, hemoglobin and reticulocyte, the time of jaundice disappearance and hospital stay in group B were significantly lower than those in group A. The level of immune cells in group B was significantly higher than that in group A after 7 days of treatment, and the levels of IgA / IgG / IgM in group B were significantly higher than those in group A after 28 days of treatment. Intravenous high-dose GG has a better effect on the condition of neonatal hemolytic disease patients, and more effectively improve the immune function of children.

P/Q-type Calcium Channel Antibodies in Lambert-Eaton Myasthenic Syndrome

Lambert-Eaton myasthenic syndrome (LEMS) is an autoimmune disease of the neuromuscular junction. Approximately 50-60% of patients with LEMS have a tumor, most often small cell lung cancer (SCLC), making LEMS a paraneoplastic neurological syndrome. In Japan, the clinical picture is a male: female ratio of 3:1; mean age, 62 years (17-80 years); and 61% of LEMS patients have SCLC (SCLC-LEMS), with the remainder of patients having no cancer. Patients with LEMS develop a unique set of clinical characteristics, which include proximal muscle weakness, depressed tendon reflexes with post-tetanic potentiation, and autonomic symptoms. Interestingly, less than 10% of patients with LEMS have cerebellar ataxia (LEMS with paraneoplastic cerebellar degeneration). Considering its pathomechanisms, LEMS is a presynaptic disorder of neuromuscular transmission in which quantal release of acetylcholine is impaired by autoantibodies against P/Q-type voltage-gated calcium channels (P/Q-VGCCs) at active zones reducing quantal release of acetylcholine, although an animal model using immunization with purified P/Q-VGCCs has not yet been established. The diagnosis can be confirmed by finding a reduced compound muscle action potential amplitude that increases by over 60% following maximum voluntary activation or 50 Hz nerve stimulation. Approximately 90% of patients who satisfy the above electrophysiological diagnostic criteria are positive for P/Q-VGCC antibodies have their diagnosis confirmed. Specific tumor therapy in SCLC-LEMS will often improve the neurologic deficit. Tumor removal is the primary treatment for LEMS. If primary tumor screening is negative, screening should be repeated after 3-6 months, followed by screening every 6 months until 2 years post diagnosis. Most patients benefit from 3,4-diaminopyridine being administered with pyridostigmine. In those with severe weakness, high-dose intravenous gamma-globulin (IVIg) or plasmapheresis confers short-term benefits. Prednisone, alone or combined with immunosuppressive drugs, can achieve long-term control of the disorder. The results of a prospective cohort study showed that the presence of LEMS with SCLC had a significant survival advantage independent of other prognostic factors including disease extent, age, sex, performance status, and serum sodium values.

A case of neuropsychiatric lupus Erythematosus characterized by the Owl\u2019s eye sign: a case report

BackgroundSystemic lupus erythematosus (SLE) is an autoimmune inflammatory disorder characterized by multiple affected systems. More than half of SLE patients will suffer from neuropsychiatric lupus erythematosus (NPSLE) during the course of their disease. Although nearly half of the NPSLE patients have normal MRI manifestations, the abnormalities found in the remainder can be located anywhere in the brain, and especially in the subcortical white matter of the frontal and temporal lobe. However, NPSLE involving the medulla oblongata and spinal cord which presents as the “owl’s eye” sign has to our best knowledge not been reported to date.Case presentationA 19-year-old girl presented at our hospital with a 7-day history of fever and headache since a one day’s exertion, accompanied by 2 days of weakness. The patient had slurred speech. Neurological examination revealed the presence of horizontal nystagmus and a limitation of bilateral eye movement when looking up and down. At the same time, she showed difficulty in raising the jaw, accompanied by a weak pharyngeal reflex. Muscle strength was remarkably decreased in all four extremities: the MRCS grade of the upper limbs was 4/5, while in the lower limbs it was 0/5. Hypotonia was apparent in the lower extremities. Regarding subjective sensation, the patient appeared to be experiencing an increased sense of pain in the whole body, and especially in the cervical region, abdomen, and feet. An examination of shallow reflex documented the reinforcement of the abdominal reflex. Deep tendon reflexes were symmetric: absent in lower, normal in upper extremities. The patient also had a stiff neck with a positive Kernig’s sign. The laboratory examination showed elevated C - reactive protein and rheumatoid factor, as well as complement components 3 and 4. Symptomatic treatments were applied, but she did not respond well, after which we did immunological laboratory examinations. The results showed the presence of anti-nRNP/Sm, anti-dsDNA and anti-AMA M2 antibodies. An MRI scan and enhancement of the cervical and thoracic regions displayed abnormal signs in the medulla and bilateral anterior horn of the lower thoracic spine. Following the exclusion of other possible diseases, neuropsychiatric lupus was diagnosed. High-dose intravenous gamma-globulin combined with methylprednisolone gradually improved her condition.ConclusionWe report the first case of NPSLE presenting with medulla oblongata and spinal cord involvement, manifesting as the “owl’s eye” sign in MRI.

Complete Response of severe idiopathic thrombocytopenic purpura after resection of bulky chromophobe renal cell carcinoma

Idiopathic thrombocytopenic purpura (ITP) associated with renal cell carcinoma (RCC) is relatively rare. In almost all of these case reports, patients affected with ITP developed differentially-involved cancer, because resection of cancer could not improve thrombocytopenia and the treatment of ITP needed to be continued after surgery. We report the case of a 48-year-old woman with massive renal cell carcinoma, measuring approximately 20 × 14 × 14 cm, who presented with severe thrombocytopenia: platelet count, 2000 cells/µl. After confirming normal bone-marrow, she received high-dose dexamethasone and intravenous gamma globulin, which rose the platelet count to normal levels. She then underwent left radical nephrectomy. The pathological examination revealed chromophobe RCC. After the resection, the platelet count was maintained within the normal range without any treatments. The current case is the first report of chromophobe RCC causative of severe ITP and the second case who achieved a sustained complete remission of ITP after cancer surgery alone; moreover our case is only one patient without other causes of ITP.

Clinical characteristics and follow-up of pediatric patients with neuromyelitis optica and neuromyelitis optica spectrum disorders

To analyze the clinical characteristics of pediatric neuromyelitis optica (NMO) and neuromyelitis optica spectrum disorders (NMOSD). A retrospective analysis was performed evaluating clinical and laboratory characteristics of ten NMO and NMOSD children who were seen in our hospital from December 2010 to May 2014. Median age at onset was 8.9 years (range 0.8-13.8 years). Seven cases were female and three were male. Median disease duration was 1.5 months (range 1-18.5 months). Eight patients fulfilled diagnostic criteria for NMO and two patients fulfilled diagnostic criteria for NMOSD. The two NMOSD patients had recurrent longitudinally extensive transverse myelitis. Four cases had a monophasic disease course, and six cases had a recurrent course. In eight NMO patients, neuritis was the initial presentation. The two NMOSD patients had no neuritis in the first attack. Nine cases had clinical manifestations of myelitis, one case had asymptomatic spinal cord MRI anomaly. Among the ten patients, seven cases had brain lesions, wherein, four cases had the midbrain involvement and in four cases extensive hemispheric white matter was involved. Three cases had medullary involvement. And two cases had posterior limb of the internal capsule involvement, two cases had thalamus involvement. In one case there was pons, cerebellum or corpus callosum involvement, respectively. One case had accompanied brain symptoms. Of the five patients who had symptomatic brain lesions, four cases had encephalopathy accompanied by large hemispheric lesions on MRI, having a presentation similar to acute disseminated encephalomyelitis. And one case had multiple sclerosis like brain lesion. Of the ten patients tested, nine were seropositive for anti-aquaporin-4 autoantibody. One-patient was complicated with systemic lupus erythematosus. Oligoclonal bands were negative in all cases. All patients received treatment for acute attacks with high-dose intravenous methylprednisolone and intravenous gammaglobulin. The symptoms of 8 cases mitigated. Two cases whose symptoms showed no sign of improvement received plasmapheresis for acute attacks. Seven of the patients were followed up. The median duration of follow-up was 19 months (ranged from 13 months to 30 months). The median Expanded disability status (EDSS) score was 3 (range 1-7). Pediatric NMO and(or) NMOSD have a diverse clinical presentation which are more than just optic neuritis and transverse myelitis, including brain symptom. So it may be difficult to distinguish NMO and( or) NMOSD from acute disseminating encephalomyelitis and multiple sclerosis in the early stages of the disease. Antibodies to aquapoin-4 (AQP-Ab) testing is very important for differential diagnosis.

The study of clinical applying continuous hemofiltration in children severe hand-foot-and-mouth disease with cardiopulmonary failure

Objective To analyze the clinical value of continuous veno-venous hemofiltration (CVVH) treatment in children with severe hand-foot-and-mouth disease (HFMD) complicated with cardio-pulmonary failure, via the prognostic comparison of the general comprehensive treatment and CVVH add-on treatment. Methods Fifty-one cases of severe HFMD with cardiopulmonary failure were divided into a CVVH group (n=19) and a control group (n=32) based on whether CVVH add-on or not. Their physiological and biochemical indicators were recorded and pediatric critical illness score (PCIS) and pediatric risk of mortality score (PRISM III) were calculated within 24 hours, when they were diagnosed with neurogenic pulmonary edema (NPE) /pulmonary hemorrhage. Both groups were treated with endotracheal intubation, mechanical ventilation with high PEEP, corticosteroids, ulinastatin, actively lowering the intracranial pressure, fluid resuscitation, milrinone, dopamine and other vasoactive drugs, high-dose intravenous gamma globulin, the CVVH group were added with CVVH treatment (duration>12 h). Prognosis difference of CVVH add-on treatment after diagnosed with NPE/pulmonary hemorrhage by tracking indicators of the third day. Survival analysis between two groups were compared by 3-day survival rates, 7-day survival rates, 28-day survival rates and the finally survival rates. Results (1) The overall conditions of two groups were comparable when diagnosed with NPE/pulmonary hemorrhage. PCIS, PRISM III, WBC counting, lactic acid, micro-blood sugar, myocardial enzymes and liver enzymes showed no significant difference between two groups. Three days after treatment, WBC and lactic acid decreased, but there was no significant difference (P>0.05), the remaining indicators had significantly improved in the CVVH group than those in the control group (P<0.05). (2) The 3-day survival rate, 7-day survival rate, 28-day survival rate and the finally survival rates in control group and CVVH group were 40.63 % vs.84.21%, 37.50% vs.73.68%, 25.00% vs.63.16%, 18.75% vs.52.63%, the survival rate in CVVH group were significantly higher (P<0.05). (3) The survival curve indicated that the survival time of CVVH group was significantly longer than that of the control group, the median survival time were 17 d and 2 d, respectively, and the difference was statistically significant (P<0.05). (4) In the CVVH group, 15 cases received CVVH after diagnosed with NPE/pulmonary hemorrhage within 12 hours, of which 10 cases (66.67%) ultimately survived, while the other 4 cases received CVVH after 12 h were all end to death, the difference was statistically significant (P<0.05). Further analysis of the impact of the timing of blood purification on the prognosis of children showed that the mortality rates of children received CVVH within 6 hours, 6 to 12 hours, after 12 hours of diagnosis of NPE/pulmonary hemorrhage, were 2/8, 3/7, 4/4, respectively. Conclusion Continuous hemofiltration can significantly improve the prognosis of children with severe HFMD, and may be preferable to perform in early stage. Key words: Continuous hemofiltration; Severe hand-foot-mouth disease; Cardiopulmonary failure; Children

Research of immunoglobulin-resistant Kawasaki disease

High-dose intravenous gamma globulin (2 g/kg) combined with oral aspirin is currently considered as standard strategy for Kawasaki disease(KD) in initial treatment.However, there are still 15%-25% of KD patients with no response to the treatment, thus leading to persistent fever, or even further damage of the coronary arteries.International literature have also mentioned other methods of treatment, such as corticosteroids, TNF-α blockade, lyclosporin, IL-1 receptor blockade, methotrexate, anti-CD20 rituximab, plasma exchange.But fixed standard for non-reactive gamma globulin require for further treatment. Key words: Kawasaki disease; Intravenous gamma globulin resistant; Glucocorticosteroid; Infliximab

Association of high-dose intravenous gamma globulin with necrotizing enterocolitis in the treatment of ABO hemolytic disease of the newborn

Objective To explore the association of high-dose intravenous gamma globulin with necrotizing enterdcolitis in the treatment of ABO hemolytic disease of the newborn.Methods 100 cases of ABO hemolytic disease of the newborn who had been treated in our hospital were selected.58 were male and 42 were female and they aged between one month to one year.According to the digital form,the infants were randomly divided into a control group and a study group,50 for each group.The control group received routine treatment; while the study group received high-dose intravenous gamma globulin in addition to routine treatment.The clinical efficacy of the therapy and the association of high-dose intravenous gamma globulin with necrotizing enterocolitis were anaalyzed by using statistical theory.Results After a period of treatment and nursing,the total bilirubin level was at higher baseline level in the study group,and time to jaundice disappearance was shorter in the study group than in the control group.Necrotizing enterocolitis was diagnosed in 10 infants in the study group and in 2 in the control group.After surgical and medical treatment,one infant died of severe intestinal necrosis and 2 died of short bowel syndrome.Conclusions Intravenous high-dose gamma globulin has certain association with necrotizing enterocolitis in the treatment of ABO hemolytic disease of the newborn; however,it has a better clinical efficacy. Key words: ABO hemolytic disease; Newborn; Necrotizing enterocolitis; Intravenous immunoglobulin; Association; Research

Six patients with Kawasaki disease showing retropharyngeal low‐density areas on computed tomography

Six patients with Kawasaki disease showing retropharyngeal low‐density areas on computed tomography

特発性血小板減少性紫斑病(ITP)に対するγ-グロブリン大量投与後の後治療の効果について

特発性血小板減少性紫斑病(ITP)に対するγ-グロブリン大量投与後の後治療の効果について

Intravenous high-dose gammaglobulins for intractable childhood epilepsy.

Immunological mechanisms have been implicated in the pathogenesis of epileptic seizures in some patients and in experimental animal models of epilepsy. A beneficial effect of high dose intravenous gammaglobulin (IVIG) has been demonstrated for some children with intractable epilepsy. In this study we treated 9 children ages 1.1-9.2 years (mean 5.0 years) with intractable epilepsy not responsive to conventional antiepileptic drugs (AEDs) and steroid therapy. Eight children had Lennox-Gastaut syndrome and 1 had complex partial seizures with secondary generalization. Each child received 3 doses of IVIG (200 mg/kg of polyvalent immunoglobulin) on Days 1, 15 and 36. Concomitant AEDs were not changed. Four children had complete remission, 3 had partial response with a more than 50% reduction in seizure frequency and 2 had no response. Onset of response varied from immediate to 7 months after the last injection. No toxicity was noted. Duration of remission was 9 months in 1 case. The other 3 cases have remained in remission to date with a follow up period of 22-26 months. We conclude that IVIG is a safe therapy which appears to be effective in some children with intractable seizures. Children with shorter duration of their seizure disorder (< 1 year) and relatively preserved cognitive function (IQ > 70) appear to have a more favorable response. Larger scale controlled trials are needed to determine the optimal timing and dosage, as well as to identify specific subgroups which may benefit most from IVIG treatment.

Autoimmune Thrombocytopenic Purpura in a Patient with Renal Clear Cell Carcinoma

A case of renal clear cell carcinoma associated with autoimmune thrombocytopenic purpura is reported. A 56-year-old man presented as thrombocytopenia (10,000/microl) was diagnosed as idiopathic thrombocytopenic purpura after certain tests. He was started on large dose of steroid, intravenous gamma globulin, TPO and multiple platelet transfusion. Platelet count was not stable. Then computerized tomography revealed a left renal tumor 46×25×31mm3. Based on the diagnosis of left renal neoplasm, left nephrectomy with preoperative high-dose intravenous gamma globulin and platelet transfusion was performed. Pathological examination revealed clear cell carcinoma. After the operation, the platelet count increased gradually. But the tumor metastasized 4 months later. Therefore, we consider that extensive tests shall be run to exclude cancer before confirming diagnosis of ITP, the elder patients, or the patients with poor therapeutic efficacy or cortisone dependent. We do not recommend using Cs as the treatment for Cancer-related ITP-like Syndrome. The tumor should be controlled first as soon as possible. If the cancer is localized, IVIG and platelet transfusion can be an appropriate initial treatment for upgrading platelet counts quickly to win time for surgery.

Thrombotic Microangiopathy After ABO-Incompatible Living Donor Liver Transplantation: A Case Report

Thrombotic microangiopathy (TMA) has rarely been reported in the setting of liver transplantation. Herein we have reported a successful case of TMA after ABO-incompatible living donor liver transplantation (LDLT) treated with plasma exchange and high-dose intravenous gamma-globulin infusion. A 50-year-old woman was diagnosed with hepatitis C virus-related cirrhosis. We performed an ABO-incompatible LDLT (group B to O) with preoperative plasma exchange to reduce the anti-B hemagglutinin titers to 1:8. The immunosuppressants consisted of tacrolimus, mycophenolate mofetil, and steroid. On postoperative day (POD) 8, her anti-B hemagglutinin titer suddenly increased to 1:64. The serum lactate dehydrogenase (LDH) level was grossly elevated (1518 IU/L). On POD 13, we suspected infection of an intra-abdominal hematoma ( Serratia marcescens) which was drained surgically. On day 5 after the reoperation, thrombocytopenia developed with a platelet count of 3×10 4/mm 3. A peripheral blood film showed severe red blood cell (RBC) fragmentation. Thus, we made a clinical diagnosis of TMA and reduced the tacrolimus dose. We started intensive daily plasma exchange (4 L/d) with fresh frozen plasma and high-dose intravenous gamma-globulin infusions. One week thereafter, thrombocytopenia improved with reduced transfusion requirements. The peripheral blood film showed normal RBC morphology. The serum LDH returned to baseline levels. Four factors were considered to have caused TMA in this case: the prescription of tacrolimus, ABO-incompatible liver transplantation, bacterial infection, and surgical stress. These factors may have all contributed by causing significant endothelial injury and TMA.

Very severe thrombocytopenia and fragmentation hemolysis mimicking thrombotic thrombocytopenic purpura associated with a giant intracardiac vegetation infected with Staphylococcus epidermidis: Role of monocyte procoagulant activity induced by bacterial supernatant

The pathogenesis of very severe thrombocytopenia in bacterial endocarditis is uncertain. We report a 50-year-old male with platelet counts < 10 x 10(9)/l and fragmentation hemolysis complicating Staphylococcus epidermidis pacemaker endocarditis with a giant vegetation. Antibiotics, corticosteroids, high-dose intravenous gammaglobulin, and plasmapheresis (for initially-suspected thrombotic thrombocytopenic purpura) failed to produce significant platelet count increase. However, therapeutic-dose heparin anticoagulation was associated with a platelet count increase from <10 to approximately 40 x 10(9)/l, with parallel reduction in thrombin-antithrombin complexes (from 8.9 to 3.5 microg/l), facilitating surgical intervention. The thrombocytopenia promptly resolved following surgical removal of the vegetation. Culture supernatant from S. epidermidis isolated from the patient's blood induced monocytes to express procoagulant activity (assessed by factor Xa generation) equivalent to lipopolysaccharide (1 microg/ml), with half-maximal activation seen with culture supernatant diluted to 1:12,800. These data are consistent with previous animal models of endocarditis demonstrating staphylococci-induced procoagulant changes in monocytes. This case demonstrates that heparin anticoagulation can be therapeutic in infective endocarditis-associated severe thrombocytopenia in a non-bleeding patient, and that such therapy may ameliorate the platelet count enough to permit surgical intervention.

Efficacy and safety of Etanercept, high-dose intravenous gammaglobulin and plasmapheresis combined therapy for lupus diffuse proliferative nephritis complicating pregnancy

We report one case of pregnancy-onset severe diffuse proliferative nephritis in a patient with systemic lupus erythematosus (SLE), who was successfully treated with a combination of anti-tumour necrosis factor (TNF)-alpha, plasmapheresis and high-dose intravenous gammaglobulin. No flares were observed either in clinical symptoms or in laboratory examinations during pregnancy or after delivery. Her autoantibodies except fluorescent anti-nuclear antibodies were negative. We suggest that a combination of anti-TNF-alpha, plasmapheresis and high-dose intravenous gammaglobulin may be a safe and effective therapy for pregnant patients suffering severe lupus nephritis.

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.

High-dose intravenous immunoglobulin for the treatment of MuSK antibody-positive seronegative myasthenia gravis

We treated two patients with anti-muscle specific tyrosine kinase (MuSK)-antibody positive seronegative myasthenia gravis (MG) with high-dose intravenous gammaglobulin (IVIg) and evaluated their clinical courses. Both patients were Japanese women, MuSK-positive seronegative MG, and were unresponsive to conventional treatments, including thymectomy, steroids, and tacrolimus. The patients required frequent hospitalization for plasmapheresis. In case 1, a 45-year-old woman, it was difficult to obtain blood access for plasmapheresis. High-dose IVIg, 400 mg/kg per day for 5 days, was administered in cases 1 and 2. In both cases, clinical improvement was observed 3 days after the start of IVIg therapy and lasted for 2 to 3 months. We propose that IVIg therapy is an effective treatment for MuSK-positive seronegative MG, when conventional treatments have failed.