Bibliography April 04

1. AGANNA E, HAWKINS PN, OZEN S, PETTERSSON T, BYBEE A, MCKEE SA, LACHMANN HJ, KARENKO L, RANKI A, BAKKALOGLU A, BESBAS N, TOPALOGLU R, HOFFMAN HM, HITMAN GA, WOO P, MCDERMOTT MF: Allelic variants in genes associated with hereditary periodic fever syndromes as susceptibility factors for reactive systemic AA amyloidosis. Genes Immun .: 2004
   Organism: 1Unit of Molecular Medicine, Department of Diabetes and Metabolic Medicine, Barts and London, Queen Mary's School of Medicine and Dentistry, Whitechapel, London, UK
   Abstract: We investigated the hypothesis that low-penetrance mutations in genes (TNFRSF1A, MEFV and NALP3/CIAS1) associated with hereditary periodic fever syndromes (HPFs) might be risk factors for AA amyloidosis among patients with chronic inflammatory disorders, including rheumatoid arthritis (RA), juvenile idiopathic arthritis (JIA), Crohn's disease, undiagnosed recurrent fevers and HPFs themselves. Four of 67 patients with RA plus amyloidosis had MEFV variants compared with none of 34 RA patients without amyloid (P value=0.03). The E148Q variant of MEFV was present in two of the three patients with TNF receptor-associated periodic syndrome (TRAPS) complicated by amyloid in two separate multiplex TRAPS families containing 5 and 16 affected members respectively, and the single patient with Muckle-Wells syndrome who had amyloidosis was homozygous for this variant. The R92Q variant of TNFRSF1A was present in two of 61 JIA patients with amyloidosis, and none of 31 nonamyloidotic JIA patients. No HPF gene mutations were found in 130 healthy control subjects. Although allelic variants in HPFs genes are not major susceptibility factors for AA amyloidosis in chronic inflammatory disease, low-penetrance variants of MEFV and TNFRSF1A may have clinically significant proinflammatory effects.Genes and Immunity advance online publication, 8 April 2004; doi:10.1038/sj.gene.6364070

2. ALSUFYANI K, ORTIZ-ALVAREZ O, CABRAL DA, LORI B, PETTY RE, MALLESON PN: The role of subcutaneous administration of methotrexate in children with juvenile idiopathic arthritis who have failed oral methotrexate. Rinsho Ganka 31:1 179-182, 2004
   Abstract: Objective. To describe the outcome of patients with juvenile idiopathic arthritis (JIA) treated with subcutaneous (Sc) methotrexate (MTX) after failing oral MTX (either because of inefficacy or toxicity) in a clinic population. Methods. The study cohort was identified from our clinical database, and consisted of 61 children with JIA treated with MTX between 1988-2001. All patients fulfilled International League Against Rheumatism (ILAR) criteria for JIA and had disease duration of gtoreq 6 months and 3 or more active joints before institution of MTX. All patients had a core set of outcome variables assessed at baseline and at 3 months after achieving both maximum oral and SC MTX. Outcome variables included physician global assessment of disease activity, number of active joints, number of joints with limited range of motion, duration of early morning stiffness, and erythrocyte sedimentation rate (ESR). Improvement was defined as at least 30% improvement from baseline in 3 of 5 variables in the core set, with no more than one of the remaining variables worsening by more than 30%. Results. A total of 61 patients, 43 females and 18 males with JIA were studied. The disease subtypes were systemic 8, polyarticular 25 (12 rheumatoid factor positive), oligoarticular 14, enthesitis related arthritis 5, and unclassified 4. Thirty-one patients were switched to SC MTX, 13 of whom had not improved, and 18 who had improved, but had nausea (11) or insufficient clinical improvement (7). After 3 months of SC MTX treatment, 76% of patients were classified as improved and 23% as not improved. Toxicity on SC MTX was less than on oral MTX. Conclusion. Our results suggest that for patients failing oral MTX either because of inefficacy or toxicity, the use of SC MTX has a high likelihood of success with more than 70% of patients achieving clinically significant improvement, without clinically significant toxicity

3. CHEN CY, CHEN LC, YEH KW, OU LS, YANG MH, HUANG JL: Sequential changes to clinical parameters and adhesion molecules following intravenous pulse cyclophosphamide and methylprednisolone treatment of refractory juvenile idiopathic arthritis. Clin Exp Rheumatol 22:2 259-264, 2004
   Organism: Division of Allergy, Asthma, and Rheumatology, Department of Pediatrics, Chang Gung Children's Hospital, Chang Gung University, Kweishan, Taoyuan, TaiwanFAU - Chen, C Y
   Abstract: It is believed that the systemic subtype and the positive rheumatoid factor, polyarticular subtype of juvenile idiopathic arthritis (JIA) show the least favorable outcomes for therapy; patients with systemic JIA are often resistant to recommended therapeutic modalities. We report the sequential changes to clinical and laboratory findings from pulse therapy with monthly intravenous cyclophosphamide (0.5 g/m2 body surface area) administration combined with methylprednisolone (30 mg/kg; 1 gm maximum) for 6 months, following which the medication interval was elongated to 3 months for a total of from 7 to 12 courses. Among 4 children suffering from refractory systemic JIA, 3 demonstrated clinical improvement, 2 of whom achieved clinical remission. Furthermore, we also adminstered this therapy to a girl suffering from refractory polyarticular JIA, following which she revealed clinical remission subsequent to 9 courses of such therapy. From our experience, we suggest that patients afflicted with JIA that is unresponsive to traditional medication may experience benefit from this type of pulse therapy

4. CHOI J, AHN M, HO S, LEE Y, KIM I, IL Y, BAE S, KIM T: Autologous peripheral blood stem cell transplantation in refractory autoimmune diseases. Blood 102:11 484b, 2003
   Abstract: Background: Autologous stem cell transplantation (ASCT) has been proposed as a new therapeutic option for patients with severe autoimmune disease refractory to conventional treatment. Methods: To evaluate the safety and efficacy of ASCT, we treated 8 autoimmune disease (2 SLE, 1 RA, 3 systemic sclerosis, 1 overlap syndrome (SLE+RA), 1 Still's disease) with ASCT. Stem cells were collected with cyclophosphamide (3g/m2) and G-CSF (300ug/m2/day) and CD34+ cells selected with Clinimacs device. The conditioning regimens were cyclophosphamide (200mg/kg)+ATG (20mg/kg for 3 days) for 7 patients and BEAM (BCNU, etoposide, cytosine arabinoside, melphalan) for 1 patient. Results: 7 female and 1 male patients were treated. The median age was 35 (22-55). The duration of underlying disease were 1-10 years. Total numbers of MNC and CD34+ cells were 4.59X108/kg (1.1-11.68) and 14.33X106/kg (1.6-30.64), respectively. Neutrophil (ANC >500/mm3) and platelet (>20,000/mm3) recovery occurred by 9 (7-12) and 6 (0-18) days after ASCT. The conditioning regimen was well tolerated. Seven patients experienced neutropenic fever but well controlled by broad spectrum antibiotics and there was no treatment related mortality during ASCT. One patient with Still's disease had a flare-up during administration of G-CSF for mobilization. The median follow-up were 27 months (6-39+). Six out of seven patients showed improvement in the health-related quality of life, which was measured by Korean Short Form Health Survey-36 (KSF-36) and EuroQol-5 Dimensions (KEQ-5D). And the functional disability, which was assessed by the Korean Health Assessment Questionnaire-20 (KHAQ-20), also showed an improvement after ASCT. One SLE who has refractory polyserositis improved dramatically 1 month after ASCT, but relapsed rapidly at 9 weeks. One SLE with nephritic syndrome and one overlap syndrome achieved complete response for 13M+ and 9M+, respectively and one scleroderma maintained with almost complete response for 15 months. Conclusions: In refractory autoimmune disease patients, ASCT can be performed safely with marked improvement and sustained withdrawal of all immunosuppressive medication. A further randomized trial and long-term follow-up is needed to confirm the efficacy and durability of remission

5. DE K, I, PRAKKEN BP, ALBANI SALVATORE, KUIS W, VAN EDEN W: The development of immune therapy with HSP60 for juvenile idiopathic arthritis
   <BOOK> Heat shock proteins and inflammation
   <SERIES> Progress in Inflammation Research. 97-108,

6. DEKKER L, ARMBRUST W, RADEMAKER CMA, PRAKKEN B, KUIS W, WULFFRAAT NM: Safety of anti-TNFalpha therapy in children with juvenile idiopathic arthritis. Clinical and Experimental Rheumatology (Italy ) 22:2 252-258, 2004
   Abstract: Anti-TNFalpha agents are frequently used in the treatment of severe JIA. Etanercept, a fully human soluble recombinant tumour necrosis factor p75 receptor Fc fusion protein, has been registered for the treatment of polyarticular course JIA patients who fail to respond to or do not tolerate methotrexate (MTX). Infliximab, a chimeric human-mouse monoclonal antibody to TNFalpha, is expected to be registered soon for JIA and Crohn's disease (CD) in children. As in adults, both agents are effective in controlling inflammation and inhibiting the progression of joint destruction. Despite this good clinical efficacy, the physician must remain alert for potential side effects, especially after prolonged use. This review gives an overview of the reported adverse events. (c) Copyright Clinical and Experimental Rheumatology 2004

7. FARPOUR-LAMBERT NJ, KELLER-MARCHAND L, RIZZOLI R, SCHWITZGEBEL V, DUBUIS JM, HANS D, HOFER MF, SUTER S: [In Process Citation]. Rev Med Suisse Romande 124:2 73-75, 2004
   Organism: Division d'endocrinologie et diabetologie pediatriques Departement de pediatrie Hopitaux Universitaires, Geneve nathaliefarpourlambert@hcugechFAU - Farpour-Lambert, Nathalie J
   Abstract: Children with chronic diseases are at increased risk of sub-optimal bone mineral acquisition and osteoporosis, especially those who have a growth and pubertal delay, reduced physical activity, inadequate nutrition, malabsorption or take medications which may influence bone development. Weight-bearing physical activity has a beneficial effect on bone development of healthy children but little is known in children with chronic diseases. Preliminary results of our cross-sectional study in children with juvenile idiopathic arthritis (JIA) suggest that hip bone mineral density is positively related with physical fitness and muscle strength and is reduced at the more affected side. We have initiated two randomized controlled trials to determine the effects of a moderate impact exercise training program on bone mineral density of children with JIA and type 1 diabetes mellitus

8. FAVALLI EG, ARREGHINI M, ARNOLDI C, PANNI B, MARCHESONI A, TOSI S, PONTIKAKI I: Anti-tumor necrosis factor alpha switching in rheumatoid arthritis and juvenile chronic arthritis [2]. Arthritis Care and Research (United States ) 51:2 301-302, 2004

9. FOELL D, WITTKOWSKI H, HAMMERSCHMIDT I, WULFFRAAT N, SCHMELING H, FROSCH M, HORNEFF G, KUIS W, SORG C, ROTH J: Monitoring neutrophil activation in juvenile rheumatoid arthritis by S100A12 serum concentrations. Arthritis Rheum 50:4 1286-1295, 2004
   Organism: Institute of Experimental Dermatology and Department of Pediatrics, University of Muenster, Muenster, Germany dfoell@uni-muensterdeFAU - Foell, Dirk
   Abstract: OBJECTIVE: Phagocytes are extensively involved in the synovial inflammation associated with chronic arthritis. The aim of our study was to determine neutrophil activation in juvenile rheumatoid arthritis (JRA) by analyzing S100A12 (EN-RAGE; calgranulin C), a proinflammatory protein secreted by human neutrophils. METHODS: S100A12 serum concentrations were determined in 124 patients with chronic active polyarticular-, oligoarticular-, or systemic-onset JRA. S100A12 was also analyzed in synovial fluid obtained from 22 patients. Changes in S100A12 levels in response to anti-tumor necrosis factor alpha (anti-TNF alpha) therapy, intraarticular injections of corticosteroids, and methotrexate (MTX) treatment were analyzed. Forty-five patients were followed up after successful antiinflammatory treatment, for a mean period of 2.8 years. RESULTS: The mean serum level of S100A12 was 395 ng/ml in patients with active polyarticular JRA and 325 ng/ml in patients with active oligoarticular JRA (normal <120 ng/ml). The level of S100A12 was approximately 10-fold higher in synovial fluid than in serum, indicating release at sites of local inflammation. In patients with systemic-onset JRA, the mean level of S100A12 was 3,700 ng/ml. Moreover, serum levels decreased in response to different antiinflammatory therapies (i.e., intraarticular injections of corticosteroids, MTX, or etanercept). S100A12 levels were elevated in 20 patients who experienced disease flares after the initial induction of remission, even weeks before the relapses became clinically apparent. CONCLUSION: S100A12 serum concentrations indicate neutrophil activation in JRA and correlate with disease activity. S100A12 may indicate synovial inflammation even when other signs of arthritis are absent. Its function as a proinflammatory factor secreted by activated neutrophils makes this protein a potential target for future therapies

10. GARRALDA ME, RANGEL L: Impairment and coping in children and adolescents with chronic fatigue syndrome: A comparative study with other paediatric disorders. Journal of Child Psychology and Psychiatry 45:3 543-552, 2004
    Abstract: Background: Functional impairment is a key feature of chronic fatigue syndrome (CFS) of childhood. Aim: To compare impairment, illness attitudes and coping mechanisms in childhood CFS and in other paediatric disorders. Method: Participants were 28 children and adolescents with CFS, 30 with juvenile idiopathic arthritis (JIA) and 27 with emotional disorders (ED). The measures used were interviews with children and parents, with detailed enquiry on impairment, including the Functional Disability Inventory (FDI), Illness Attitudes Scales (IAS), and Kidcope to measure coping styles in relation to common problems, illness and disability. Results: Children with CFS reported significantly more illness impairment, especially in school attendance, than those with JIA and ED. They had higher 'worry about illness' scores on the IAS. On the Kidcope they named school issues (work, expectations, attendance) as illness- or disability-related problems more than the other two groups. Fewer CFS participants reported using problem solving as a strategy to cope with illness and disability than with other problems in their lives. More in the CFS than in the JIA group used emotional regulation to cope with illness and disability. Fewer in the CFS than in the ED groups used social withdrawal to cope with illness and self-criticism for disability, but more used resignation to cope with disability. Conclusion: Severe illness-related impairment, particularly through school non-attendance, and high levels of illness-related school concerns appear specific to CFS. CFS may also have characteristically high levels of generalised illness worry and particular styles of coping with illness and disability

11. HASEGAWA D, MANABE A, ISHIKAWA KUMIKO_(REPRINT), WADA M, YAGASAKI H, YOSHIMASU TETSU_(REPRINT), OHTSUKA Y, TSURUTA TOSHIHISA_(REPRINT), KAWASAKI H, EBIHARA YASUHIRO_(REPRINT), NAKAHATA T, TSUJI K: Diminished erythroid colony formation in juvenile myelomonocytic leukemia. Blood 102:11 328b, 2003
    Abstract: Juvenile myelomonocytic leukemia (JMML) is a rare disease with clonal abnormality of the pluripotent hematopoietic stem cell, and its common laboratory findings are leukocytosis with monocytosis, thrombocytopenia, and anemia. The diagnosis of JMML, however, is not always easy to make, because clinical and morphological findings of JMML can be mimicked by several viral infections including Epstein-Barr virus (EBV), cytomegalovirus (CMV), human herpes virus 6 (HHV6), especially in early infancy when the most of patients with JMML are diagnosed. In addition, selective hypersensitivity to granulocyte-macrophage colony-stimulating factor (GM-CSF) of myeloid progenitor cells, which is included in diagnostic criteria for JMML, has been reported in patients with viral infections. To further define the diagnostic features that help to discriminate JMML from other reactive processes, we performed a prospective analysis of in vitro cell culture with bone marrow progenitor cells from patients suspected of having JMML. Materials; Bone marrow samples were obtained from 30 children who were suspected of having JMML, through the registration of the MDS committee of the Japanese Society of Pediatric Hematology. Informed consent was obtained from guardians of patients. They were finally diagnosed with; JMML (n=21), refractory anemia (n=2), acute myelogenous leukemia (n=1), atypical chronic myelogenous leukemia (n=1), hemophagocytic syndrome (n=1), infectious diseases (n=3), and systemic type-juvenile idiopathic arthritis (n=1). Methods; Mononuclear cells (MNC) were separated by density gradient centrifugation on Ficoll-Paque from heparinized bone marrow samples. Each sample containing 2X104 MNCs was added with GM-CSF, concentration of which ranged from 0.01ng/ml to 10 ng/ml in order to obtain dose-response assay, or cocktail of cytokines (10ng/ml for GM-CSF, 100 ng/ml for stem cell factor; SCF, 20 ng/ml for IL-3, 100 ng/ml for IL-6, and 2U/ml for erythropoietin; EPO), or no cytokine. Cultures were performed in duplicates, and the number of colonies consisting of more than 40 cells was scored after 14 days of incubation. Results; All patients in non-JMML group had a normal erythroid colony formation in the presence of cytokine cocktail, but neither hypersensitivity to GM-CSF nor spontaneous colony formation was observed, except for one patient with CMV infection who had both hypersensitivity to GM-CSF and spontaneous colony formation. In contrast, patients with JMML, most of them had aberrant GM-colony formation, showed a markedly decreased eryhtroid colony formation. Median erythroid colony ratio (erythroid colony count in all the colonies) of JMML and non-JMML was 0.3% and 40.0%, respectively (P<0.01, Mann-Whitney test). Discussion; JMML is a clonal disorder of the pluripotent stem cell, and growth of the normal hematopoietic progenitors are impaired. The dysplastic feature of erythroid precursors and elevated fetal hemoglobin are frequently found in patients with JMML, but the pathogenesis of dyserythropoiesis remains to be clarified. In our study, in vitro erythroid colony formation was severely suppressed in patients with JMML. We speculate that aberrant GM clones which have the hypersensitivity to GM-CSF inhibit in vitro erythropoiesis. In addition to aberrant GM-colony formation, to examine the capability of erythroid colony formation may be helpful to discriminate JMML from other reactive processes, including viral infections

12. HORNEFF G, SCHMELING H, BIEDERMANN T, FOELDVARI I, GANSER G, GIRSCHICK HJ, HOSBACH T, HUPPERTZ HI, KEITZER R, KUESTER RM, MICHELS H, MOEBIUS D, ROGALSKI B, THON A: The German Etanercept Registry for Treatment of Juvenile Idiopathic Arthritis (JIA). Ann Rheum Dis .: 2004
    Organism: University of Halle, Germany
    Abstract: BACKGROUND: Etanercept has been approved for refractory polyarticular JIA following a randomised controlled study involving 69 patients. Long term data in a larger cohort of children are missing. OBJECTIVE: To evaluate long-term feasibility, safety and efficacy, a registry was set up to prospectively monitor children treated with etanercept in Germany and Austria. METHODS: Giannini's criteria, the duration of morning stiffness, the number of swollen, tender and contracted joints, adverse events and reasons for discontinuation were assessed. RESULTS: So far 322 patients with JIA were included and 12 additional patients with non-JIA rheumatic diagnoses were followed for safety evaluation. Therapeutic efficacy was noted 1 month after therapy was started. The number of patients with significant improvement as well as the strength of improvement further increased during the first year of treatment. The mean+/- SD of morning stiffness decreased from 45+/- 65 min to 12+/-30 and 7+/-19 after 1 and 3 months, respectively, and remained low thereafter (p<0.001 for all points in time). The mean+/- SD of the number of tender and swollen joints decreased from 9+/-9 and 8.4+/- 9 to 3.0+/-6.5 and 4.5+/-7 respectively after 1 month and 2.2+/-5.5 and 3.3+/-5.5 after 3 months and remained low thereafter. According to Gianinni's criteria of 30%, 50% and 70%, a therapeutic response was achieved with 66%, 54% and 30% after 1 month, 78%, 61% and 38% at 3 months and 83%, 72% and 52% of JIA patients after 6 months of therapy, and remained stable thereafter. Subtype analysis revealed a marked lower therapeutic efficacy in patients with systemic onset arthritis. At 6 months of therapy 56% of these did reach the 30% response criteria, 44% the 50% criteria, in contrast to 88% of non-systemic JIA patients who met the 30% and 78% the 50% efficacy level. Overall tolerability was good. In 592 patient treatment years there were 69 reports on adverse events in 56 patients including one CNS demyelinisation. There were no opportunistic infections or lupus-like reactions. 53 JIA patients discontinued therapy; 25 because of lack of efficacy. 14 of them were diagnosed with systemic arthritis. Treatment as discontinued in 12 patients after long-term remission was achieved. In 16 patients the drug was discontinued for other reasons. CONCLUSION: Etanercept treatment was safe and led to a significant improvement in the vast majority of JIA-patients resistant to conventional treatment

13. KITTISARAPONG K, THAVONPANICH N_(REPRINT), BENJAPOLPITAK S, BASILE G: CINCA syndrome (chronic infantile neurological cutaneous articular syndrome). A case report of a superficial resemblance to systemic-onset JRA with mutation in CIAS 1 gene from Thailand. Journal of Allergy and Clinical Immunology 113:2 Supplement S132, 2004

14. LEE H, YIM D, NESTOROV I, ZHOU H, BUCKWALTER M, PECK C: 0.8 Mg/Kg once weekly subcutaneous regimen of etanercept will yield an overlapping steady state time-concentration profile with 0.4 mg/Kg twice weekly dosing in pediatric patients with juvenile rheumatoid arthritis (JRA). Clinical Pharmacology & Therapeutics 75:2 53, 2004

15. LEE T, CHAN GC, SHAU Y, HO H, CHIANG AK, LAU Y: Autologous stem cell transplant in 3 patients with refractory autoimmune diseases. Blood 102:11 484b-485b, 2003
    Abstract: Objective: To determine the safety and efficacy of immune ablation and autologous hematopoietic stem cell transplantation (HSCT) in severe systemic lupus erythematosus (SLE) and refractory juvenile idiopathic arthritis (JIA). Methods: Two patients with persistently active SLE after oral cyclophosphamide therapy and one patient with rheumatoid factor negative polyarticular JIA refractory to prednisolone, subcutaneous methotrexate, intravenous immunoglobulin and oral cyclophosphamide were recruited for HSCT. T-cells depletion was performed by CD-34 positive selection (Isolex) from the patients' bone marrow cells. The conditioning regimen used was cyclophosphamide (160-200 mg/kg), antithymocyte globulin (90 mg/kg), and fractionated total body irradiation (4.42Gy). Outcome was evaluated by serum complement levels, serologic markers, function of diseased organs, and immunosuppressive medication requirements. Results: The two patients with SLE were 20 years old and 21 years old respectively and the child with JIA was 11 years old. The mean follow-up duration after HSCT was 16 months (range 9-26 months). All patients were alive with gradual but significant improvement. Complement and anti-double stranded DNA levels normalized with marked improvements in end organ functions for the two SLE subjects. Joint pain and morning stiffness resolved totally for the JIA patient (except bilateral hip osteoarthritic pain due to avascular necrosis before HSCT). Immunosuppresive medications were stopped in 2 patients (SLE/JIA). The other SLE patient is taking prednisolone 5mg alternate day only. They all have good performance status (Karnofsky score 90 for 2 SLE patients and Lansky score 80 for JIA patient). Conclusion: In patients experiencing the persistence of organ-threatening lupus or refractory JIA following standard, aggressive therapy, HSCT may be performed safely, with marked clinical improvement and sustained withdrawal of all immunosuppressive medication(s). A phase III randomized trial is warranted to determine the relative efficacy and durability of remission of HSCT compared with standard therapies

16. LOTITO AP, CAMPOS LM, DIAS MH, SILVA CA: [Reflex sympathetic dystrophy]. J Pediatr (Rio J) 80:2 159-162, 2004
    Organism: Universidade de Sao Paulo (USP), Sao Paulo, SP, BrazilFAU - Lotito, Ana P N
    Abstract: OBJECTIVE: To describe eight patients with reflex sympathetic dystrophy in terms of clinical and laboratory characteristics and treatment. DESCRIPTION: Eight children (four girls) with reflex sympathetic dystrophy were retrospectively analyzed. The diagnosis of reflex sympathetic dystrophy was based on the presence of pain in the distal extremities, local edema, vasomotor instability and impairment of sensibility. Two patients had associated systemic lupus erythematosus, one had juvenile idiopathic arthritis and one had Glanzmanns thrombasthenia. Mean age was 11.5 years. Most of the patients had lower extremity involvement (7/8). The most important clinical signs were pain, edema and vasomotor instability in the affected extremity (8/8), functional impairment (7/8), and impaired sensibility (3/7). The erythrocyte sedimentation rate was abnormal in three patients and the bone scans in five. All patients received non-steroidal anti-inflammatory drugs and physical therapy with improvement of the symptoms in seven patients, until six months of treatment. Three patients were submitted to acupuncture with good response. One patient had a severe disease and received tricyclic antidepressants, with improvement more than one year after. COMMENTS: Reflex sympathetic dystrophy should be included as part of the differential diagnosis of limb pains of childhood, so that physicians can make an earlier diagnosis and prevent functional impairment

17. MALLESON PN, OEN K, CABRAL DA, PETTY RE, ROSENBERG AM, CHEANG M: Predictors of Pain in Children with Established Juvenile Rheumatoid Arthritis. Arthritis Care and Research (United States ) 51:2 222-227, 2004
    Abstract: Objective. To examine demographic and disease-related variables that affect pain in a large cohort of patients with juvenile rheumatoid arthritis (JRA). Methods. Selection criteria were an onset of JRA >=5 years prior to study and age >=B years at the time of the study. Pain was measured by a self-administered 10-cm visual analog scale. Possible explanatory variables studied included age at study, sex, race, onset subtype, active disease duration, active joint count, and physician's global assessment (PGA). Results. In a multiple regression model, active disease duration, PGA, and age at study were independent predictors explaining 22% of the variation in pain scores. Stratified analyses showed an effect of age in the 8-15-year group, but not in older patients. Conclusion. Disease-related factors explain only a small proportion of the variation in pain scores. Age has an effect on pain scores only in younger patients. The role of other factors, including psychosocial factors, needs further study

18. MCNEILL T: Fathers' experience of parenting a child with juvenile rheumatoid arthritis. Qual Health Res 14:4 526-545, 2004
    Organism: The Hospital for Sick Children, Toronto, CanadaFAU - McNeill, Ted
    Abstract: The author examined the experience of fathers who have a child with juvenile rheumatoid arthritis (JRA). He used grounded theory methodology, in which 22 fathers participated in semistructured interviews, and developed a substantive theory of fathers' experience that addresses the impact of their child's JRA, their adaptational responses, and the meanings they associated with their experiences. Fathers were profoundly affected, perceived their child's condition as a catalyst for meaningful involvement, experienced many emotions, and sought to adopt a positive approach to making sense of their child's condition. Fathers' efforts to be strong for others resulted in an overreliance on self-support strategies, particularly during periods of high stress. Given the nature of fathers' experience and the extent of their involvement, greater attention by health care practitioners to fathers' adaptation is indicated

19. MOHR W: Joint Sarcoidosis in Childhood
    GELENKSARKOIDOSE IM KINDESALTER. Aktuelle Rheumatologie (Germany ) 29:1 50-52, 2004
    Abstract: Childhood sarcoidosis is a rarely disease of unknown etiology. In children less than 4 years a clinical triad of rash, polyarthritis and uveitis is characteristic. Nevertheless, these clinical symptoms may be misdiagnosed as juvenile chronic arthritis as described in the case report. The final diagnosis in the presented case was done by histopathology on a synovectomy specimen exhibiting epithelioid granulomata. The case report indicates that joint biopsy may be diagnostic for differentiation of childhood sarcoidosis and juvenile chronic arthritis

20. NIEHUES T, HORNEFF G, MICHELS H, SAILER HM, SCHUCHMANN L: [Evidence-based use of Methotrexate in children with rheumatic disorders]. Z Rheumatol 63:2 147-159, 2004
    Organism: Padiatrische Immunologie und Rheumatologie Klinik fur Kinder-Onkologie-Hamatologie und Immunologie Zentrum fur Kinder- und Jugendmedizin, Heinrich-Heine-Universitat Dusseldorf, Moorenstrasse 5, 40225, Dusseldorf, Germany, niehues@uni-duesseldorfdeFAU - Niehues, T
    Abstract: Juvenile idiopathic arthritis (JIA) is the most common diagnosis in children and adolescents with rheumatic disorders. In many children and adolescents, JIA is successfully treated with nonsteroidal antiinflammatory drugs (NSAR) and physiotherapy. Still, in a significant number of cases the disease is resistant to this therapy and treatment with "second line" disease modifying antirheumatic drugs (DMARDs) is required. Methotrexate (MTX) is frequently referred to as "first choice second line agent" for the treatment of JIA. However, there are considerable differences among pediatric rheumatologists on how and when to use MTX. To increase drug safety, the Working Group for Children and Adolescents with Rheumatic Diseases in Germany (AGKJR) and the Working Group Pediatric Rheumatology Austria have initiated the formulation of evidence-based recommendations. Evidence is based on consensus expert meetings, a MEDLINE search with the key words "Methotrexate" and "juvenile arthritis" limited to age 0-18 years, standard textbooks and review articles, data from the central registry of the German Research Center for Rheumatic Diseases (Deutsches Rheumaforschungszentrum Berlin), experience with MTX in adults with rheumatoid arthritis (RA) and recommendations of the German Society of Rheumatology (DGRh). Based on these data, evidence and recommendations are graded and evidence-based recommendations for the use of MTX in children and adolescents with rheumatic disease are presented

21. PAEGLE DI, HOLMLUND AB, OSTLUND MR, GRILLNER L: The occurrence of antibodies against Chlamydia species in patients with monoarthritis and chronic closed lock of the temporomandibular joint. J Oral Maxillofac Surg 62:4 435-439, 2004
    Organism: Department of Oral and Maxillofacial Surgery, Karolinska Institutet, Huddinge, SwedenFAU - Paegle, Diana I
    Abstract: PURPOSE: The study goal was to investigate the occurrence of serum antibodies to Chlamydia trachomatis, Chlamydia pneumoniae, and Chlamydia psittaci in patients with temporomandibular joint (TMJ) monoarthritis or chronic closed lock and in control subjects. PATIENTS AND METHODS: An indirect microimmunofluorescence test for detecting antibodies against C trachomatis was used. Twenty-three patients (12 with monoarthritis and 11 with chronic closed lock) and 42 control subjects were evaluated. RESULTS: Six patients with monoarthritis, 5 patients with chronic closed lock of the TMJ, and 6 control individuals were considered to have had a past C trachomatis infection based on their immunoglobulin G titers. Corresponding groups for C pneumoniae investigation included 3 patients with monoarthritis, 4 patients with chronic closed lock, and 17 control subjects, and for C psittaci, 1 patient with monoarthritis, 2 patients with chronic closed lock, and 1 control subject. Statistically significant differences between patients and control subjects were found for C trachomatis only; monoarthritis versus control (P =.016), chronic closed lock versus control (P =.038), and all patients versus control (P =.007). Patients with monoarthritis did not differ from patients with chronic closed lock with regard to antibodies against C trachomatis. CONCLUSION: The occurrence of serum antibodies to C trachomatis was significantly higher in patients than in control subjects, but this occurrence did not correlate with severity of observed tissue changes. Nevertheless, an association may exist between the presence of C trachomatis and TMJ disease

22. ROTH J, PALM C, SCHEUNEMANN I, RANKE MB, SCHWEIZER R, DANNECKER GE: Musculoskeletal abnormalities of the forearm in patients with juvenile idiopathic arthritis relate mainly to bone geometry. Arthritis Rheum 50:4 1277-1285, 2004
    Organism: University Children's Hospital, Tuebingen, Germany johannesroth@charitedeFAU - Roth, Johannes
    Abstract: OBJECTIVE: Alterations of the skeletal system, including reduced bone mineral density, increased frequency of fractures, and changes in markers of bone metabolism, have been described in juvenile idiopathic arthritis (JIA), but measurement of volumetric bone density and bone geometry is not possible with the techniques used in most studies. This study was undertaken to obtain a more detailed understanding of the musculoskeletal system in JIA by analyzing bone density, bone geometry, and muscle force as the most important factor in bone development. METHODS: The technique of peripheral quantitative computed tomography was used in a cross-sectional study of 57 children with the oligoarticular, polyarticular, or systemic form of JIA. Density of trabecular and cortical bone as well as geometric parameters of bone and muscle were measured at the forearm. RESULTS: Children in all subgroups had significantly reduced muscle cross-sectional area, which was strongly correlated with muscle force and abnormalities in geometric parameters of bone, including a significant reduction in cortical thickness. Trabecular density was affected only in the polyarticular JIA group, and cortical density was normal in all subgroups. CONCLUSION: Our results suggest that an important problem in JIA is the lack of muscle mass and force, together with abnormal bone geometry. The thinned bony cortices might predispose to fractures even though cortical bone density itself is normal. These results might have implications with regard to therapeutic approaches to preserve musculoskeletal integrity in JIA

23. SHI J, KOVACS SJ, LUDDEN TM, BHARGAVA V: Population pharmacokinetics (PPK) analysis of A77 1726 (M1) after oral administration of leflunomide (LEF) in pediatric subjects with polyarticular course juvenile rheumatoid arthritis (JRA). Clinical Pharmacology & Therapeutics 75:2 5, 2004

24. SHIMADA Y, HORIGUCHI M, OKUBO T: Bilateral Spontaneous Hyphema with Uveitis in a Young Girl. Journal of Pediatric Ophthalmology and Strabismus (United States ) 41:2 114-115, 2004
    Abstract: A healthy 5-year-old girl presented with bilateral hyphema as an initial symptom of uveitis. The ocular findings and the patient's age suggested that the uveitis was due to juvenile rheumatic arthritis or chronic iridocyclitis

25. STUERMER T, BRENNER H, KOENIG W, GUENTHER K-P: Severity and extent of osteoarthritis and low grade systemic inflammation as assessed by high sensitivity C reactive protein. Annals of the Rheumatic Diseases 63:2 200-205, 2004
    Abstract: Background: Although osteoarthritis (OA) is thought to derive from defective chondrocyte metabolism and thus inherently lack the large scale systemic response of rheumatoid arthritis, there is increasing interest in the acute phase proteins in OA. Objective: To assess the association between high sensitivity C reactive protein (hsCRP) and severity and extent of OA in patients with advanced hip and knee OA. Methods: Preoperative hsCRP was measured in frozen serum samples from 770 consecutive patients with hip or knee joint replacement due to advanced OA recruited between 1995 and 1996. Pain was measured by a visual analogue scale and the Western Ontario and McMaster Universities OA index (WOMAC). The extent of OA in different joints was assessed clinically and radiographically. Results: The (geometric) mean hsCRP was 2.5 mg/l among all patients. Severity of pain was associated with mean hsCRP (adjusted elevation highest v lowest quintile=35%, p=0.01) after controlling for known or suspected predictors of hsCRP, including age, smoking, and body mass index. Neither the bilateral nor the generalised extent of OA, nor any of the dimensions of the WOMAC were associated with mean hsCRP levels. Conclusions: Severity of pain, but not extent of OA, was associated with hsCRP levels in this group of patients with advanced OA. Longitudinal studies with repeated assessments of hsCRP and pain are needed to assess the possible value of hsCRP for monitoring or predicting the clinical course of OA

26. SUCHOMEL P, STULIK J, KLEZL Z, CHROBOK J, LUKAS R, KRBEC M, MAGERL F: [Transarticular fixation of C1-C2: a multicenter retrospective study]. Acta Chir Orthop Traumatol Cech 71:1 6-12, 2004
    Organism: Neurochirurgicke oddeleni, Neurocentrum Nemocnice Liberec, Husova 10, 460 63 Liberee petrsuchomel@nemlibczFAU - Suchomel, P
    Abstract: PURPOSE OF THE STUDY: Transarticular C1-2 fixation is a surgical alternative in treatment of atlantoaxial instability. Although the method provides very good immediate and long-term stability, it still involves several disadvantages. The group of patients as reported from various institutions are usually very small and hardly comparable. In order to objectively compare the results of the method, we collected the groups of patients treated in four institutions dealing with surgery of the cervical spine in Czech Republic. MATERIAL AND METHODS: During the 9-years period (1993-2001), the transarticular C1/2 fixation was performed in 80 patients (mean age 45.6 years, range 4-85 years). The procedure was indicated for atlantoaxial instability due to rheumatoid arthritis in 32 cases, pseudoarthrosis of the odontoid process in 15 cases, fracture of the odontoid in 8 cases, complex C1-C2 fracture in 7 cases, tumour in 5 cases, C1 fracture in 4 cases, os odontoideum in 3 cases, purulent osteolysis of the odontoid in 3 cases and instability due to tuberculosis in one case, respectively. Two patients underwent surgery for painful arthrosis of atlantoaxial joints only. Transarticular fusion was combined with posterior interlaminar fixation using autologous graft and wire in most of the cases. Clinical and radiological results were evaluated in the early postoperative period and 3, 6 and 12 months after surgery, respectively. The position of the screws in relation to lateral mass of the atlas was evaluated according to our own criteria as optimal, suboptimal, and misplaced. Long-term postoperative stability and bone fusion were also followed. The follow-up ranged from 3 to 99 months (mean 29.1 months). There were 72 patients available for long-term follow-up (i.e. more then 6 months). RESULTS: We inserted 150 screws; two screws were used in 72 patients, one screw in 6 patients while in two patients, the surgery had to be aborted without screwing. Optimal placement was achieved in 103 cases (68.7%), suboptimal because of too medial or lateral placement of the screws in 26 cases (17.3%), suboptimal due to a short screw in 9 case (6%) and a long screw in 8 cases (5.3%). Four screws (2.7%) were found misplaced (i.e. out of the lateral masses). Fusion was confirmed in 51 cases out of 72 operated on (70.8%) at 6-months follow-up, and in 55 cases out of 63 available for follow-up (87.3%) at 12 months, respectively. Segmental stability was achieved in all patients, even in cases with incomplete fusion as seen on radiograph. Furthermore, six screws in four patients were discovered to be broken, nevertheless without any clinical consequences. There were 4 cases of peroperative injury to th vertebral artery (i.e. 5% of patients, 2.7% of screws), one case of dural tear and one case of excessive blood loss from epidural venous plexus. These complications, however, did not cause any significant clinical consequences, either. Other postoperative complications included wound dehiscence in 3 cases, 2 cases of hardware failure due to wrong indication for surgery and 2 cases of persistent neck pain. DISCUSSION: Transarticular C1/2 fixation is known to be universal and stable technique suitable for the treatment of atlantoaxial instability. According to biomechanical studies, this method provides the best stability mainly in rotation and lateral flexion (inclination) when compared to other described methods of atlantoaxial fixation. The fusion rate is reported to vary between 90 to 100% if the posterior interlaminar fusion using bone graft and wire is simultaneously performed. The rare incidence of pseudarthrosis is usually considered to be related to a poor surgical technique as even only one screw should provide bone fusion if properly placed. Using strict evaluation criteria, the fusion rate in our sample of patients was 87.3% at 12 months, or, 92.1% if also controversial radiographs were included. The injury to the vertebral artery is the most serious complication of the method; its incidence in our group (5% of patients) is comparable to data from literature. We believe that most of these events happened because of individual anatomical variations of axis and vertebral artery were not adequately respected. CONCLUSION: Transarticular technique of instrumental atlantoaxial fusion is an effective method with multiple application in treatment of craniocervical and upper cervical spine instability. The gain of immediate stability with acceptable risk of possible complications is the major advantage of this procedure. The results of our multicentric retrospective study confirm the expected high fusion rate and are comparable to previously published reports

27. TUTAR E, EKICI F, NACAR N, ARICI S, ATALAY S: Delayed maculopapular, urticarial rash due to infliximab in two children with systemic onset juvenile idiopathic arthritis. Rheumatology (Oxford) 43:5 674-675, 2004

28. YIM D, LEE H, NETOROV I, ZHOU H, BUCKWALTER M, PECK CC: A population pharmacokinetic (PK) analysis of etanercept in patients with juvenile rheumatoid arthritis (JRA). Clinical Pharmacology & Therapeutics 75:2 53, 2004

29. ZHOU H, PATAT A, PARKS V, BUCKWALTER M, METZGER D, KORTH-BRADLEY J: Absence of a Pharmacokinetic Interaction between Etanercept and Warfarin. J Clin Pharmacol 44:5 543-550, 2004
    Organism: Clinical Pharmacology, Wyeth Research, 500 Arcola Road, Collegeville, PA 19426FAU - Zhou, Honghui
    Abstract: Etanercept, a soluble recombinant human tumor necrosis factor receptor (TNFr) fusion protein, is effective and well tolerated in the treatment of rheumatoid arthritis (RA), juvenile rheumatoid arthritis (JRA), psoriatic arthritis (PsA), and ankylosing spondylitis (AS). The primary objective of this study was to investigate the potential pharmacokinetic and pharmacodynamic interaction between a single dose of R- and S-enantiomers of warfarin and multiple doses of etanercept after administration of warfarin and etanercept alone and together. In a nonrandomized, three-period study, 12 healthy male subjects received a single oral 25-mg dose of warfarin after an overnight fast, followed by twice-weekly 25-mg subcutaneous doses of etanercept for seven doses. The last dose of etanercept was administered concurrently with a second dose of warfarin. Serial blood samples for plasma warfarin concentration measurement and international normalized ratio (INR) assessment were collected before and up to 144 hours after dose administration. Serial blood samples for serum etanercept concentration measurement were collected before and up to 60 hours after the sixth dose and 264 hours after the seventh dose. Etanercept did not affect the pharmacokinetics and pharmacodynamics of warfarin. All ratios of maximum serum concentration (C(max)) and area under the serum concentration versus time curve (AUC) for pharmacokinetics (R- and S-enantiomers of warfarin) and INR fell within the confidence interval of 0.8 to 1.25. Warfarin also did not cause a clinically significant alteration in the pharmacokinetics of etanercept. In conclusion, coadministration of etanercept and warfarin would not be expected to change the pharmacokinetics of either medication; therefore, no dosage adjustment is needed in cases in which warfarin and etanercept are coadministered