Yukoh Aihara

Efficacy and safety of tocilizumab in patients with systemic-onset juvenile idiopathic arthritis: a randomised, double-blind, placebo-controlled, withdrawal phase III trial.

BACKGROUNDnSystemic-onset juvenile idiopathic arthritis does not always respond to available treatments, including antitumour necrosis factor agents. We investigated the efficacy and safety of tocilizumab, an anti-interleukin-6-receptor monoclonal antibody, in children with this disorder.nnnMETHODSn56 children (aged 2-19 years) with disease refractory to conventional treatment were given three doses of tocilizumab 8 mg/kg every 2 weeks during a 6-week open-label lead-in phase. Patients achieving an American College of Rheumatology Pediatric (ACR Pedi) 30 response and a C-reactive protein concentration (CRP) of less than 5 mg/L were randomly assigned to receive placebo or to continue tocilizumab treatment for 12 weeks or until withdrawal for rescue medication in a double-blind phase. The primary endpoint of the double-blind phase was an ACR Pedi 30 response and CRP concentration of less than 15 mg/L. Patients responding to tocilizumab and needing further treatment were enrolled in an open-label extension phase for at least 48 weeks. The analysis was done by intention to treat. This study is registered with ClinicalTrials.gov, numbers NCT00144599 (for the open-label lead-in and double-blind phases) and NCT00144612 (for the open-label extension phase).nnnFINDINGSnAt the end of the open-label lead-in phase, ACR Pedi 30, 50, and 70 responses were achieved by 51 (91%), 48 (86%), and 38 (68%) patients, respectively. 43 patients continued to the double-blind phase and were included in the efficacy analysis. Four (17%) of 23 patients in the placebo group maintained an ACR Pedi 30 response and a CRP concentration of less than 15 mg/L compared with 16 (80%) of 20 in the tocilizumab group (p<0.0001). By week 48 of the open-label extension phase, ACR Pedi 30, 50, and 70 responses were achieved by 47 (98%), 45 (94%), and 43 (90%) of 48 patients, respectively. Serious adverse events were anaphylactoid reaction, gastrointestinal haemorrhage, bronchitis, and gastroenteritis.nnnINTERPRETATIONnTocilizumab is effective in children with systemic-onset juvenile idiopathic arthritis. It might therefore be a suitable treatment in the control of this disorder, which has so far been difficult to manage.

Carbamazepine‐induced hypersensitivity syndrome associated with transient hypogammaglobulinaemia and reactivation of human herpesvirus 6 infection demonstrated by real‐time quantitative polymerase chain reaction

Summary Drug‐induced hypersensitivity syndrome (HS) is a rare but severe disease with multiorgan failure. Many different precipitating factors have been reported, but the pathophysiology of HS remains unknown. However, the association of the human herpesvirus (HHV) family, particularly of HHV‐6, has recently been reported in patients with HS. We report a 14‐year‐old boy who was diagnosed as having carbamazepine‐induced HS based on the clinical course, laboratory data and results of drug‐induced lymphocyte stimulation tests. In addition, the reactivation of HHV‐6 was demonstrated by real‐time quantitative polymerase chain reaction and by significantly increased levels of the specific antibody in his paired sera. Furthermore, transient hypogammaglobulinaemia was detected in the early stage of the disease. In addition, serum levels of interferon‐γ, interleukin (IL)‐6, IL‐5 and eosinophil cationic protein, which were increased on admission, decreased dramatically after steroid therapy. This is the first report of carbamazepine‐induced HS associated with reactivation of HHV‐6, transient hypogammaglobulinaemia, increased serum levels of inflammatory cytokines and activated eosinophils. This case might contribute to the understanding of the pathophysiology of HS.

DEMONSTRATION OF MOTHER-TO-INFANT TRANSMISSION OF HEPATITIS B VIRUS BY MEANS OF POLYMERASE CHAIN REACTION

To investigate the failure of vaccines to prevent mother-to-infant transmission of hepatitis B virus (HBV), serum, cord blood, and colostrum samples from eleven mothers, known to be carriers of hepatitis B surface antigen, and their infants were examined by means of a highly sensitive polymerase chain reaction (PCR) method. HBV-specific DNA was detected in ten maternal serum samples, eight samples of colostral whey, eight samples of colostral cells, and one cord blood sample. Four infants of mothers with HBV-DNA-positive colostrum showed low responsiveness to hepatitis B vaccine. The infant whose cord blood was positive for HBV DNA showed low responsiveness to hepatitis B vaccine and subsequently became an HBV carrier. These results suggest the need for further study to evaluate whether breastfeeding is advisable for HBV carriers.

In vitro antigenic reactivity of synthetic lipid a analogues as determined by monoclonal and conventional antibodies

Cross-reactivities of synthetic lipid A analogues with monoclonal and conventional antibodies against Salmonella lipid A were studied. It was shown that the in vitro antigenicity of a synthetic compound 506, beta-(1----6) D-glucosamine disaccharide 1,4-bisphosphate, which is acylated at 2-amino and 3-hydroxyl groups with (R)-3-dodecanoyloxytetradecanoyl and (R)-3-tetradecanoyloxytetradecanoyl groups, respectively, and has (R)-3-hydroxytetradecanoyl groups at 2-amino and 3-hydroxyl groups, was practically indistinguishable from that of the natural E. coli lipid A preparation, and that both phosphates in positions 1 and 4 as well as ester- and amide-linked fatty acyl residues, particularly 3-acyloxyacyl group, of the glucosamine disaccharide are involved in the cross-reactivity of lipid A as important antigenic determinants.

Successful Treatment of Onychomycosis with Fluconazole in Two Patients with Hyperimmunoglobulin E Syndrome

Abstract: We report two patients with hyperimmunoglobulin E syndrome who had fingernail onychomycosis and were successfully treated with fluconazole. Relapse of oral candidiasis, but not of onychomycosis, was observed within three months of stopping fluconazole. There were no adverse effects from this therapy. Based on our experience, we think that fluconazole may be useful in the treatment of onychomycosis in patients with hyper‐lgE syndrome as well as in those with other primary immunodeficiency disorders.

Acute leucoencephalopathy during cyclosporin A therapy in a patient with nephrotic syndrome

A 13-year-old girl with nephrotic syndrome (NS) developed acute leucoencephalopathy during combination therapy with cyclosporin A (CyA) and prednisolone (PSL). The patient had a generalized motor seizure followed by coma at 19 days after CyA administration. Magnetic resonance scanning performed on the 1st hospital day revealed white matter lesions in the subcortices of the parietal and occipital lobes, brain stem and cerebellum. These lesions had completely resolved on the 10th hospital day. This episode might be caused by CyA because the clinical course and laboratory data revealed neither inflammation nor other causative factors. To our knowledge, this is the first report of acute leucoencephalopathy during combination therapy with CyA and PSL in a patient with NS.

Effects of liposteroid on skin lesions in autoimmune MRLlpr/lpr mice

Dexamethasone palmitate (D-PAL) incorporated into lipid microspheres (D-PAL emulsion) is taken up by the reticuloendothelial system and by some inflammatory cells. Therefore, it has a stronger anti-inflammatory activity than free corticosteroids in vivo. To study the effect of D-PAL emulsion on systemic lupus erythematosus (SLE), we administered D-PAL emulsion to MRLlpr/lpr mice, an animal model for human SLE. The effect of D-PAL emulsion was compared with that of methylprednisolone (m-PSL), a water-soluble steroid. Percent survival was higher in the group treated with 0.25 mg of D-PAL emulsion intravenously once every 4 weeks than in those groups treated similarly with m-PSL or PBS control. Swelling of lymph nodes was frequent in the group treated with m-PSL or with PBS, while rarely observed in the group treated with D-PAL emulsion. Proteinuria was more frequent in the groups treated with m-PSL or PBS than in the group treated with D-PAL emulsion. Although the frequency of skin lesions was not different between these three groups, the control and m-PSL treated mice had severe skin lesions, such as hair loss of erythematous skin with scales and crusts at the nape, while D-PAL emulsion treated animals showed only facial alopecia without inflammatory skin changes. These data demonstrate that D-PAL emulsion was more effective than a corresponding dose of m-PSL on autoimmune prone mice. This suggests that intermittent administration of D-PAL emulsion may be effective in the treatment of human SLE.

Analysis of antigenic reactivity of synthetic monosaccharide lipid A analogues with monoclonal antibodies

In vitro antigenic reactivity of chemically synthesized monosaccharide analogues of nonreducing sugar moiety of lipid A with 4 monoclonal antibodies against Salmonella minnesota R595 lipid A was studied by the inhibition test of enzyme-linked immunosorbent assay (ELISA). In the assays with 2 monoclonal antibodies (mAb 5G and mAb36G), which have been suggested to recognize the Salmonella type lipid A structure, no antigenic reactivity of the tested analogues was observed. However, several monosaccharide analogues exhibited antigenic reactivities with other monoclonal antibodies (mAb161M and mAb19M), especially some structural differences of hydrophobic and/or hydrophilic parts among monosaccharide analogues were recognized by mAb161M.

Whole blood interferon‐γ assay for tuberculosis in children in Japan

Background:u2002 Whole blood interferon‐γ assay QuantiFERON‐TB2G (QFT‐2G), which is a new specific method for diagnosing tuberculosis (TB), has been developed and used in the clinical field. The aim of the present study was to assess the usefulness of QFT‐2G as an indicator, both for diagnosing childhood TB and for assessing therapeutic effectiveness.

Transient remission of intractable systemic-type of juvenile rheumatoid arthritis after chickenpox in a 2-year-old boy.

collagen diseases in children.1 However, the pathogenesis of the disease remains unclear. We sometimes experience intractable cases with a systemic-type of JRA, which is refractory to several antirheumatic drugs, including acetyl salicylic acid (ASA), prednisolone (PSL), gold, methotrexate (MTX) and even cyclosporine A (CsA). In contrast, chickenpox is a common infectious disease in children. Chickenpox rarely presents with any severe complications, such as hemophagocytic syndrome.2 Recently, we experienced a case of intractable systemictype JRA, who went into transient remission after contracting chickenpox. To our knowledge, this type of phenomenon in JRA has not been previously reported and this case may contribute to the understanding of the pathogenesis of the disease, including the importance of the balance between T helper (Th) 1 and Th2 cells in JRA, and to develop a new therapeutic strategy for the treatment of the condition.