Safety and efficacy of long-term etanercept in the treatment of methotrexate-refractory polyarticular-course juvenile idiopathic arthritis in Japan.

OBJECTIVES: Previous short-term trials found etanercept (0.2 or 0.4 mg/kg) to be effective and well tolerated in Japanese children with juvenile idiopathic arthritis (JIA) who were intolerant/resistant to methotrexate. The aim of this study was to evaluate the long-term safety and efficacy of etanercept in Japanese children with JIA. METHODS: Patients (4-19 years) who received etanercept in one of three short-term studies continued onto this long-term open-label study. RESULTS: Of the 32 patients enrolled, 18 (56.3%) completed 192 weeks of the study and 14 (43.8%) were discontinued; 7 (21.9%) for patient refusal, 2 (6.3%) for adverse events (AEs), and 5 (15.6%) for lack of efficacy. All patients reported AEs; 31 (96.9%) reported infections and 6 (18.8%) reported serious AEs. Main efficacy assessments included change from baseline in the American College of Rheumatology Pediatric core components, including mean improvements from baseline in the physician global assessment (90.7%), patient/guardian global assessments (54.1%), Childhood Health Assessment Questionnaire (84.6%), and median improvements in C-reactive protein levels (92.7%). No unexpected safety results were reported, and early efficacy responses were sustained in the long term. CONCLUSIONS: This study provides further evidence that etanercept is an effective therapeutic option for Japanese children with polyarticular-course JIA.

Definitive differences in laboratory and radiological characteristics between two subtypes of juvenile idiopathic arthritis: systemic arthritis and polyarthritis.

We performed this study to investigate the differences in radiological and laboratory findings between systemic juvenile idiopathic arthritis (s-JIA) and polyarthritis (p-JIA). Twenty-two patients with s-JIA and 18 with p-JIA were enrolled. Their laboratory findings and radiographs were examined retrospectively. Plain radiographs were obtained before the induction of biological agents. All radiographs were examined for the presence of soft tissue swelling, juxta-articular osteopenia, joint space narrowing, subchondral bone cyst, erosion, epiphyseal irregularity, and growth abnormalities. Carpal length and bone mineral density of the lumbar spine, an indicator of generalized osteoporosis, were also investigated in all the patients enrolled. Laboratory examinations involved white blood cell counts, platelets, C-reactive protein (CRP), rheumatoid factor (RF), anti-cyclic citrullinated peptide (CCP) antibody, and matrix metalloproteinase (MMP)-3. Comparisons of the laboratory findings between s-JIA and p-JIA indicated that the titers of anti-CCP antibody and RF were significantly increased in p-JIA sera (P < 0.05). There was no difference in BMD between the two groups of patients. Carpal length was significantly shorter in p-JIA patients than in s-JIA patients (P < 0.05). The most frequent radiological abnormality in s-JIA was juxta-articular osteopenia (93.8%), in comparison to a frequency of 50.0% in p-JIA. Joint space narrowing was shown in 9.8% of the s-JIA patients compared to 35.7% of the p-JIA patients. Subchondral bone cyst and erosion were more frequent in p-JIA than s-JIA. In conclusion, there were differences in radiographic characteristics and laboratory data between s-JIA and p-JIA in this study. In the radiological evaluation, bone-related abnormality was prominent in s-JIA and joint-related abnormality was striking in p-JIA, and these results indicated that the pathogenic bases of arthritis appear to differ between these two subtypes of JIA.

Survey of psychological support for bereaved families in Japan.

BACKGROUND: The aim of the present study was to investigate the current conditions of psychological support for the families of children who died suddenly of disease or accident. METHODS: A questionnaire survey was conducted in 2415 medical facilities across the country that have at least 100 beds and are staffed by pediatricians. Of these, 981 facilities (40.6%) responded to the questionnaire. RESULTS: There were 653 infant deaths soon after admission in 254 facilities (25.9%). For pronouncement of death, approximately 43% of the pediatricians made no attempt to provide psychological support for the family members affected. In contrast, some 53% of the pediatricians did offer psychological support. In self-assessments, approximately 53% of the pediatricians stated that the support was 'not very satisfactory' or 'unsatisfactory', while only 28% considered that they were 'fully satisfied with the help being given'. Reasons for this response were appropriate specialized knowledge, and enough time for such tasks. The proportion of institutions that employed staff specializing in psychological support for families was only 7%. Approximately 83% of institutions without such specialist staff, however, acknowledged the need for them. The number of medical facilities that gave information regarding family support associations to bereaved families was very low (11%). CONCLUSION: Psychological support for families of children who died shortly after entering hospital cannot be characterized as satisfactory. The provision of grief care by family associations is desirable, and the cooperation of the institutions and family associations is important.

Whole blood interferon-gamma assay for tuberculosis in children in Japan.

BACKGROUND: Whole blood interferon-gamma 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. METHODS: The subjects were 61 children introduced to the TB outpatient department for the first time between June 2004 and March 2006. QFT-2G, the tuberculin test and chest computed tomography (CT) were performed for all patients. RESULTS: Ten patients having typical characteristics of primary tuberculosis (PTB) on chest CT, and diagnosed as having tubercle bacillus infections, all had positive reaction on QFT-2G. Of seven patients who had no abnormalities on diagnostic imaging but who reacted positively on QFT-2G, one developed TB later, and no TB was detected over the period of observation in 44 patients with negative QFT-2G at their first consultation. Moreover, four patients with non-tuberculous acid-fast bacilli in which Mycobacterium avium or Mycobacterium gordonae was detected had negative reaction on QFT-2G. In addition, all 10 patients with positive reactions on QFT-2G in whom the subsequent course of the disease was observed had decrease on QFT after treatment. CONCLUSIONS: QFT-2G is a powerful tool with a wide application both in diagnosis and in assessment of treatment effectiveness in PTB.

[Clinical features and laboratory findings in children with both anti-dsDNA and anti-U1-RNP antibody].

Mixed connective tissue disease (MCTD) includes clinical features of systemic lupus erythematosus (SLE), dermatomyositis/polymyositis (DM/PM), and systemic sclerosis (SSc) occurring in conjunction with a high anti-U1-RNP antibody titer. Childhood MCTD rarely manifests the symptoms and signs of DM/PM and SSc, and mostly does those of SLE. Thus, the diagnosis of childhood MCTD is inevitably based on the two major findings, Raynaud's phenomenon and a high titer of anti-U1-RNP antibody. However, in clinical setting there exist patients who have both anti-dsDNA antibody, a SLE disease-marker, and anti-U1-RNP antibody, a MCTD disease-marker, and thus it is hard to differentiate MCTD patients from SLE. Eighty children were enrolled in this study, and divided into 3 groups ; group A, those who are positive for anti-dsDNA antibody/negative for anti-U1-RNP antibody (48 cases, 60.0%), group B : those who are positive for both anti-dsDNA and anti-U1-RNP antibody (22 cases, 27.5%), group C; those who are negative for anti-dsDNA antibody/positive for anti-U1-RNP antibody (10 cases, 12.5%), and each of the clinical characteristics among these 3 groups was mutually examined. The results indicated that the frequency of hypocomplementemia in group B was close to group A rather than group C, and the frequencies of both hyper-gamma-globulinemia and Raynaud's phenomenon were very close to group C, but not to group A. On the contrary, the findings which seemed to be specific to MCTD, high titers of speckled type anti-nuclear antibody and rheumatoid factor, located at the middle between group A and group C. Thus, children in group B essentially carried characteristic symptoms and signs of both SLE and MCTD, and it will be difficult to differentiate these two diseases at the onset of the disease. Taken together, children with high titers of both anti-dsDNA antibody and anti-U1-RNP antibody as well as clinical symptoms and signs such as hyper-gamma-globulinemia, Raynaud's phenomenon, membranous nephritis, positive speckled type anti-nuclear antibody and rheumatoid factor should be followed and treated as children with MCTD along with SLE.