Bibliography July 05

1. ARLET JB, THI HUONG DB, POUCHOT J, PIETTE JC: Current concepts on the pathogenesis of adult-onset Still's disease. Rev Med Interne 26:7 549-556, 2005
   Organism: Service de medecine interne, groupe hospitalier Pitie-Salpetriere, 83, boulevard de l'Hopital, 75651 Paris cedex 13, France jbarlet@libertysurffrFAU - Arlet, J B
   Abstract: PURPOSE: Adult-onset Still's disease (AOSD) is a rare systemic inflammatory disorder of unknown origin. It is characterized by hectic fever, evanescent rash, polyarthralgias or polyarthritis, sore throat, hepatosplenomegaly, lymphadenopathy, polynuclear leukocytosis, liver cytolysis, and high serum level of ferritin with low glycosylated fraction. CURRENT KWOWLEDGE AND KEY POINTS: An increased serum level of ferritin, IL-8, IL-6, IL-18 and TNF-alpha indicates that macrophages are highly activated in AOSD. Interleukin 18 (IL-18) seems to be a key cytokine in the pathogenesis of AOSD. Serum IL-18 levels are increased in AOSD patients compared to other systemic inflammatory diseases such as rheumatoid arthritis and they are well correlated with serum ferritin levels and disease activity. IL-18 could cause acute liver injury and arthritis. Macrophages could be activated by infectious agents such as viruses and by an inadequate control of T cell response secondary to depressed Natural Killer lymphocyte function, similarly to that observed in systemic juvenile idiopathic arthritis. Sustained macrophage activation can lead to the hemophagocytic syndrome, a severe complication of both AOSD and systemic juvenile idiopathic arthritis. FUTURE PROSPECTS: Cytotoxic cell functions should be probably studied in AOSD as they were in the hemophagocytic syndrome and systemic juvenile idiopathic arthritis because AOSD, characterised by a marked macrophage activation may be related to an immunological deficiency

2. ARLET JB, BOUTIN-LE THI HD, POUCHOT J, PIETTE JC: Current concepts on the pathogenesis of adult-onset Still's disease
   PHYSIOPATHOLOGIE DE LA MALADIE DE STILL DE L'ADULTE. Revue de Medecine Interne (France ) 26:7 549-556, 2005
   Abstract: Purpose. - Adult-onset Still's disease (AOSD) is a rare systemic inflammatory disorder of unknown origin. It is characterized by hectic fever, evanescent rash, polyarthralgias or polyarthritis, sore throat, hepatosplenomegaly, lymphadenopathy, polynuclear leukocytosis, liver cytolysis, and high serum level of ferritin with low glycosylated fraction. Current kwowledge and key points. - An increased serum level of ferritin, IL-8, IL-6, IL-18 and TNF-alpha indicates that macrophages are highly activated in AOSD. Interleukin 18 (IL-18) seems to be a key cytokine in the pathogenesis of AOSD. Serum IL-18 levels are increased in AOSD patients compared to other systemic inflammatory diseases such as rheumatoid arthritis and they are well correlated with serum ferritin levels and disease activity. IL-18 could cause acute liver injury and arthritis. Macrophages could be activated by infectious agents such as viruses and by an inadequate control of T cell response secondary to depressed Natural Killer lymphocyte function, similarly to that observed in systemic juvenile idiopathic arthritis. Sustained macrophage activation can lead to the hemophagocytic syndrome, a severe complication of both AOSD and systemic juvenile idiopathic arthritis. Future prospects. - Cytotoxic cell functions should be probably studied in AOSD as they were in the hemophagocytic syndrome and systemic juvenile idiopathic arthritis because AOSD, characterised by a marked macrophage activation may be related to an immunological deficiency. (c) 2004 Elsevier SAS. Tous droits reserves

3. BRADLEY JD, DMITRIENKO AA, KIVITZ AJ, GLUCK OS, WEAVER AL, WIESENHUTTER C, MYERS SL, SIDES GD: A randomized, double-blinded, placebo-controlled clinical trial of LY333013, a selective inhibitor of group II secretory phospholipase A2, in the treatment of rheumatoid arthritis. J Rheumatol 32:3 417-423, 2005
   Organism: Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN 46285, USA bradleyjd@lillycomFAU - Bradley, John D
   Abstract: OBJECTIVE: To evaluate the efficacy and safety of a selective inhibitor of secretory phospholipase (sPLA2), LY333013, in the treatment of rheumatoid arthritis (RA). METHODS: Two hundred and fifty-one patients with active RA despite treatment with one or more disease modifying antirheumatic drugs (DMARD) received oral doses of LY333013 (50, 250, and 1000 mg) or placebo once daily for 12 weeks. Concomitant low-dose glucocorticoids (< or = 10 mg/day prednisone equivalent) were allowed. Clinical improvement was assessed using the response criteria of the American College of Rheumatology (ACR20), and safety was evaluated with respect to adverse events and laboratory test abnormalities. RESULTS: The demographic characteristics of the treatment groups were similar. Dose-response relationships were found for ACR20 responses (p = 0.058) and reductions in C-reactive protein (p = 0.058) at week 1. The proportions of patients with an ACR20 response subsequently increased in all study groups including the placebo group at weeks 4 and 8, and the initial treatment benefit was lost. Adverse events were generally mild in severity and not associated with treatment. CONCLUSION: Treatment with LY333013 for 12 weeks was well tolerated but ineffective as an adjunct to DMARD treatment of active RA

4. CAMARGO JF, TOBON GJ, FONSECA N, DIAZ JL, URIBE M, MOLINA F, ANAYA JM: Autoimmune rheumatic diseases in the intensive care unit: experience from a tertiary referral hospital and review of the literature. Lupus 14:4 315-320, 2005
   Organism: Rheumatology Unit, Clinica Universitaria Bolivariana, Medellin, Colombia, South AmericaFAU - Camargo, J F
   Abstract: Autoimmune rheumatic diseases (AIRD) are not uncommon in the general population and up to one third of hospitalized patients with AIRD may need admission to intensive care unit (ICU). This paper describes the causes of admission, the clinical features and outcome of 24 AIRD patients admitted to a medical ICU from a third level hospital. Thirteen patients had systemic lupus erythematosus (54.2%), three rheumatoid arthritis (12.5%), three pulmonary renal syndrome (12.5%), two dermatopolymyositis (8.3%), two scleroderma (8.3%) and one antiphospholipid syndrome (4.2%). The main causes for ICU admission were rheumatic disease flare-up (37.5%), infection (37.5%) and complications derived from rheumatic disease (29.1%). Mortality during ICU stay was 16.7% (four patients). Excluding shock requiring vasopressor support, no statistical difference was found between survivors and nonsurvivors; although there was a trend to higher test severity scores (APACHE II, ODIN) in nonsurvivors. Our results reveal a lower mortality rate in AIRD patients admitted to the ICU than reported previously. Severity scores such as APACHE II are predictors of mortality in patients with AIRD in the ICU

5. CANNON GW, HOLDEN WL, JUHAERI J, DAI W, SCARAZZINI L, STANG P: Adverse events with disease modifying antirheumatic drugs (DMARD): a cohort study of leflunomide compared with other DMARD. J Rheumatol 31:10 1906-1911, 2004
   Organism: Veterans Affairs Salt Lake City Health Care System, Division of Rheumatology, University of Utah, Salt Lake City, Utah, USA grantcannon@medvagovFAU - Cannon, Grant W
   Abstract: OBJECTIVE: To determine and compare the incidence of serious adverse events (AE) during treatment of rheumatoid arthritis (RA) with disease modifying antirheumatic drugs (DMARD), focusing on leflunomide (LEF). METHODS: A retrospective cohort study of a large US insurance claims database was performed. Study groups were patients with RA classified by DMARD exposure as either no-DMARD therapy, single-agent DMARD (monotherapy), or combination-DMARD therapy. Specific DMARD examined were leflunomide (LEF) and methotrexate (MTX), compared to other DMARD (penicillamine, hydroxychloroquine, sulfasalazine, gold, etanercept, infliximab) and no DMARD (nonsteroidal antiinflammatory drugs, COX-2 inhibitors). All AE reported were considered endpoints; primary endpoints included hepatic, dermatologic, hematologic, infectious, respiratory, hypertension, and pancreatitis AE. RESULTS: The 40,594 RA patients of the study period (September 1998 to December 2000) accumulated 83,143 person-years (PY) of followup. Followup for each of the groups was: DMARD-monotherapy, 46,054 PY (55% of total); combination-DMARD, 25,830 PY (14%); and no-DMARD, 11,259 PY (14%). The incidence rate of all AE combined was significantly lower for LEF monotherapy (94 events/1000 PY) than MTX (145 events/1000 PY), other DMARD (143 events/1000 PY), or no DMARD (383 events/1000 PY) (p < 0.001 for all comparisons). The "all-AE" rates during combination therapy with LEF + MTX (43/1000 PY) and LEF + other DMARD (59/1000 PY) were lower than the "all-AE" rate for DMARD + MTX (70/1000 PY; p = 0.002). LEF monotherapy had the lowest rate of hepatic events in the DMARD monotherapy groups. CONCLUSION: The rates of AE in the LEF group, alone and combined with MTX, were generally lower than or comparable to the AE rates seen with MTX and other agents

6. CAPARBO VF, DA SILVA CAA, PEREIRA RMR: Serum from children with Juvenile Rheumatoid Arthritis (JRA) inhibits the differentiation and increases apoptosis of human osteoblasts in culture. J Bone Miner Res 19: S334, /10/4

7. CONNELLY TW, JR.: Family functioning and hope in children with juvenile rheumatoid arthritis. MCN Am J Matern Child Nurs 30:4 245-250, 2005
   Organism: Thomas W Connelly, Jr, is an Assistant Professor, Boston College, William F Connell School of Nursing, Chestnut Hill, MA He can be reached via e-mail at conneltc@bceduFAU - Connelly, Thomas W Jr
   Abstract: PURPOSE:: To examine the relationships among family functioning, hope, and quality of life in children with juvenile rheumatoid arthritis (JRA). STUDY DESIGN AND METHOD:: Sixty-eight children (8 to 12 years of age) with a diagnosis of JRA and one of their parents/guardians participated in this descriptive correlational study. Parents completed the Feetham Family Functioning Survey (FFFS), the Parent Report for Children Pediatric Quality of Life Inventory (PedsQL), and the Parent Report for Children PedsQL Rheumatology Module. The children completed the Children's Hope Scale (CHS), the Child Report for PedsQL, and the Child Report PedsQL Rheumatology Module. Data were analyzed using chi-square, t-tests, and correlation analyses. RESULTS:: Family functioning and children's hope showed a negative correlation, indicating that a child's hope was lower when the parent reported greater dissatisfaction with family functioning. Hope was not related to parent or child ratings of the child's quality of life. CLINICAL IMPLICATIONS:: In caring for children with JRA, nurses can assess the family's satisfaction with relationships to the broader community, subsystems, and individual members and seek ways to promote healthy family functioning. Nurses also can assess the level of hope in children with JRA and facilitate the development of hopefulness by helping children establish goals and develop strategies to meet them

8. DE BENEDETTI F, FUNARI A, BERNI S, BALLANTI P, GIACINTO C, PARO R, SPICA E, RUCCI N, TETI A: Bone defects in NSE/hIL-6 mice overexpressing IL-6 reminiscent of the human systemic juvenile idiopathic arthritis. J Bone Miner Res 19: S36, /10/4

9. DELAUNAY C, MIGAUD H, JOBIN A, KERBOULL L, HAMADOUCHE M, COURPIED J-P, KERBOULL M, BIZOT P, GAUCHER F, LECLERCQ S, NIZARD R, WITVOET J, SEDEL L, PHILIPPOT R, FARIZON F, LECUIRE F, ADAM P, FESSY M-H, FLECHER X, GRISOLI D, HELIX M, CHEVROL Y, AUBANIAC J-M, ARGENSON J-N, NOURISSAT C, ASENCIO G, BERTEAUX D, VIDALAIN J-P, CARTILLIER J-C, EPINETTE J-A, LAFFARGUE P, BESSON A, DUQUENNOY A, PINOIT Y: Primary total hip replacement in active patients younger than 50 years of age
   ARTHROPLASTIE TOTALE DE HANCHE DU SUJET ACTIF DE MOINS DE 50 ANS. Revue de Chirurgie Orthopedique et Reparatrice de l'Appareil Moteur (France ) 91:4 351-374, 2005
   Abstract: Introduction More than young age, high activity level is worldwide highlighted as the major factor affecting the longevity of primary total hip replacement (THR). Aim of this multicentric French symposium was to overview the results of current prosthetic options choosen by a pannel of members of the "Hip and Knee French Society" (SFHG) to treat 1ary or 2ary hip arthritis in active and younger than 50 years old patients. Material and methods According to the selection criteria (ie., virgin or hardware-free hips, no high dysplasia > Crowe 2, no rheumatoid or juvenile arthritis, activity > Devane 2 and age < 50), 1419 1ary THRs were reviewed, performed by 12 surgical groups from 17 institutions. The majority (72%) of the 9 implant combinations had cementless fixation (89% HA coated), 15.1% were fixed with cement and 10% had hybrid fixation. Mean age was 41.2 years and activity level graded Devane 4 and 5 was reported for 55.7% of patients (inter-series range, isr, 38 to 81%). Main diagnosis were hip osteonecrosis (36%) and dysplasia in 27%. Results At 7.9 year average follow-up (isr, 6.4 to 14.2 years), overall complication rate was 2.5% and average reoperation rate was 7.3% (isr, 3.8 to 13%). Ten-year survival rate from revision for any cause was > 95% for all THR combinations except for 3: the cementless Bousquet THR (86.4%, mainly due to failure of fixation of alumina coated double cup), the cementless ABG THR (90.9%, mainly due to acetabular osteolysis of HA-coated cup with zirconia-PE bearings) and the hybrid Osteal-Cerafit THR with alumina-alumina bearings (90.4%). With revision for aseptic loosening, 10-year survivorship was < 95% for 2 THR combinations: 88.6% for the Bousquet THR and 92.3% for the Osteal-Cerafit THR, whilst up to 100% for4 cementless combinations (the ABG-HA, the Omnifit-HA and the non-HA Alloclassic-Armor or CSF cups). With bearing revision (for wear, fracture, osteolysis and dislocation or impingement), 10-year survival was < 97% only for the Zirconia-PE (94%). Discussion and conclusion The main limits of the study were its retrospective aspect except for 3 series, an average follow-up < 10 years. Nevertheless, some observations can be drawn. 1/ On the femoral side, cementing according to the "French paradox" technique remained an efficient option, at least with smooth super-steel implant like the Charnley-Kerboull stem (10-year survival from revision for aseptic lossening, 97.6%); nevertheless, in this young and active population, all 6 uncemented stems showed better survival than the 2 smooth cemented ones. 2/ On the acetabular side, except the alumina-coated Bousquet cup and the Ti-mesh Cerafit-cup, either cemented (Charnley-Kerboull) or all other cementless cups, including the threaded rings, provided 10-year survivorship > 99%. 3/ At least, the 7.9 year average follow-up was not sufficient to show any significant difference between 10-year surv ival of the various bearings used, including hard-on-hard ones (alumina-alumina 32 mm, 98.6% survival at 10 years; Metasul 28 mm, 100% survival but at 8 years only). Another decade will be necessary to allow more conclusive appraisal on this crucial matter. (c) Masson, 2005

10. EISEN GM, GOLDSTEIN JL, HANNA DB, RUBLEE DA: Meta-analysis: upper gastrointestinal tolerability of valdecoxib, a cyclooxygenase-2-specific inhibitor, compared with nonspecific nonsteroidal anti-inflammatory drugs among patients with osteoarthritis and rheumatoid arthritis. Aliment Pharmacol Ther 21:5 591-598, 2005
    Organism: Oregon Health and Science University, Portland, OR 97239, USA eiseng@ohsueduFAU - Eisen, G M
    Abstract: AIM: To compare the incidence of abdominal pain, dyspepsia and/or nausea associated with valdecoxib, nonspecific nonsteroidal anti-inflammatory drugs and placebo in patients with rheumatoid arthritis and osteoarthritis. METHODS: Data from five randomized, double-blind 12-week trials were pooled. Independent risk factors for abdominal pain, dyspepsia and/or nausea were also determined. RESULTS: The final analysis consisted of 4394 patients. Nonspecific nonsteroidal anti-inflammatory drug users (n = 1185) received naproxen 1000 mg/day (n = 766), ibuprofen 2400 mg/day (n = 207) or diclofenac sodium 150 mg/day (n = 212). Valdecoxib users received 10 mg/day (n = 955), 20 mg/day (n = 851) or 40 mg/day (n = 430). A total of 973 patients received placebo. The nonspecific nonsteroidal anti-inflammatory drug group was most likely to report abdominal pain or dyspepsia, while the placebo group reported the highest incidence of nausea. The most important risk factors for abdominal pain, dyspepsia and/or nausea were nonspecific nonsteroidal anti-inflammatory drug use, gastrointestinal history of nonspecific nonsteroidal anti-inflammatory drug-related intolerance or gastroduodenal ulcers, osteoarthritis diagnosis, female gender and age <65 years. CONCLUSION: This pooled analysis demonstrates a clear decrease in dyspepsia and an improvement in upper gastrointestinal tolerability for patients with osteoarthritis and rheumatoid arthritis taking valdecoxib, even at supratherapeutic doses, compared with those taking nonspecific nonsteroidal anti-inflammatory drugs over 12 weeks

11. GREEN MR, KENNELL AS, LARCHE MJ, SEIFERT MH, ISENBERG DA, SALAMAN MR: Natural killer cell activity in families of patients with systemic lupus erythematosus: demonstration of a killing defect in patients. Clin Exp Immunol 141:1 165-173, 2005
    Organism: Department of Immunology, Imperial College School of Medicine, London, UKFAU - Green, M R J
    Abstract: Natural killer (NK) cell cytotoxic activity and cell frequency, expressed as a percentage of total lymphocytes, have been determined in peripheral blood mononuclear cells from first-degree relatives of patients with systemic lupus erythematosus (SLE), the patients themselves, a group of rheumatoid arthritis (RA) patients and controls. Low levels of killing activity relative to controls were found in some members of all groups with the extent of depression falling into two ranges. Moderate reductions were seen in female (3/31, 10%) and male (4/14, 29%) relatives of SLE patients, female (12/60, 20%) and male (3/4, 75%) SLE patients and female RA patients (6/17, 35%). A more profound depression of killing activity was confined to other female SLE patients (15/60, 25%). There were strong correlations in all groups between killing activity and percentage of NK cells, but analysis of the ratio of these parameters and studies with purified preparations of NK cells suggest that the reduced activity in SLE frequently involves a defect in the killing capacity of the individual cells in addition to the reduced levels of NK cells. Azathioprine (AZA), which was used in treatment of 12 SLE patients, was invariably associated with low values of killing activity. It appears to substantially reduce the percentage of NK and B cells in an action unconnected with the NK cell abnormalities associated with SLE. The finding of low killing activity in relatives and a correlation between their activity and that of their patients support the view that NK cell deficiency is a genetic determinant of SLE. NK cells in SLE may produce insufficient levels of cytokines required for the regulation of IgG production

12. HAAS JP: Genes and factors influencing susceptibility to juvenile idiopathic arthritis
    GENE UND RISIKOFAKTOREN BEI DER JUVENILEN IDIOPATHISCHEN ARTHRITIS. Aktuelle Rheumatologie (Germany ) 30:3 147-152, 2005
    Abstract: Juvenile idiopathic arthritis (JIA) is not an inherited disease transmitted with a classical genetic pathway but genetic factors have reasonable influence on disease susceptibility. Within recent years, several factors have been defined affecting susceptibility and course of the disease. This review summarizes our current knowledge: 1. Affected siblings have a low concordant incidence of the disease, but a high concordance of its subtype and course. 2. Subtypes of JIA have different genetic backgrounds. 3. Some JIA patients do not carry any of the defined risk genes at all. 4. Most of the subtypes of JIA have a genetic background distinct from rheumatoid arthritis in adults. 5. There are multiple factors involved in the pathogenesis implying genetic and environmental factors. 6. Genetic factors are not only involved in disease susceptibility but also in the course of the disease and the occurrence of complications. 7. Genetic factors responsible for an increased risk of complications will have an increasing influence on therapeutic decisions. Patients and their relatives frequently ask questions addressing the pathogenesis and the risk of disease transmission within the family. Moreover, parents frequently present with a guilty feeling. Physicians have to deal with all these issues thoroughly and with great empathy for the family's situation. The knowledge of the factors involved in the pathogenesis of JIA has considerably progressed in the past decade but continues to remain a challenge. (c) Georg Thieme Verlag KG Stuttgart

13. HAFNER R: Juvenile idiopathic arthritis: When and which DMARD and how long?
    JUVENILE IDIOPATHISCHE ARTHRITIS: WANN WELCHES BASISTHERAPEUTIKUM UND WIE LANGE? Aktuelle Rheumatologie (Germany ) 30:3 187-190, 2005
    Abstract: Indication for a disease modifying antirheumatic drug (DMARD) in juvenile idiopathic arthritis (JIA) derives from the form of arthritis as well as its course. Oligoarthritis can often be treated with NSAIDs and intraarticular injections alone. A DMARD is indicated when the disease remains active for more than 6 to 12 months, when radiographic destructions appear or when problem joints like wrists or hips are involved. For polyarthritis and systemic JIA, an early start with DMARDs is important. Gold standard is methotrexate. Azathioprine or leflunomide can be alternatives if methotrexate is not well tolerated. We have good experience with antimalarials for ANA-positive oligoarthritis and sulfasalazine for enthesitis-related arthritis. Cyclosporin A is mainly used for severe uveitis. Not all DMARDs are licensed for use in children with chronic arthritis. Off-label use is therefore common in pediatric rheumatology. Combinations of DMARDs are also used in JIA, but there are no studies available. No reliable data exist for the length of DMARD therapy. Most pediatric rheumatologists treat their patients for at least one year after remission is achieved. (c) Georg Thieme Verlag KG Stuttgart

14. HENRICKSON M, REIFF A: Prolonged efficacy of etanercept in refractory enthesitis-related arthritis. J Rheumatol 31:10 2055-2061, 2004
    Organism: Division of Rheumatology, Children's Hospital Central California, Madera, California 93638-8762, USA mhenrickson@childrenscentralcalorgFAU - Henrickson, Michael
    Abstract: OBJECTIVE: For many children enthesitis-related arthritis (ERA) causes substantial morbidity, and conventional treatments frequently offer limited efficacy. Tumor necrosis factor-alpha (TNF-alpha) has been found to play a central role in the spondyloarthritides. We investigated the longterm efficacy of the TNF fusion protein etanercept in the treatment of patients with ERA refractory to disease modifying antirheumatic drug (DMARD) therapy. METHODS: Eight patients with active, inflammatory ERA were treated in an open-label pilot trial of twice weekly subcutaneous injections (dosing range of 25 to 37.5 mg twice weekly, 0.2-0.8 mg/kg/dose) of etanercept for 2 years. Outcome measures included duration of morning stiffness, active joint count, hemoglobin, and erythrocyte sedimentation rate (ESR). Patients were permitted concomitant nonsteroidal antiinflammatory drugs (NSAID) and DMARD at stable doses. RESULTS: Treatment with etanercept resulted in significant improvement in active joint count, hemoglobin, and ESR in all 8 patients within 2 months. Additionally, all patients noted increased mobility and overall well being. Improvement in morning stiffness did not achieve statistical significance. One patient was lost to followup after completing one year of the study. The remaining 7 patients had sustained statistically significant efficacy for active joint count, hemoglobin, and ESR throughout the entire 2-year trial. All patients tolerated etanercept with no side effects. CONCLUSION: Despite limited power, these results indicate that etanercept provided a rapid clinical response in our cohort of patients with refractory ERA, who achieved sustained efficacy over a 2-year period

15. HENTGEN V, DESPERT V, LEPRETRE AC, CUISSET L, CHEVRANT-BRETON J, JEGO P, CHALES G, GALL EL, DELPECH M, GRATEAU G: Intrafamilial variable phenotypic expression of a CIAS1 mutation: from Muckle-Wells to chronic infantile neurological cutaneous and articular syndrome. J Rheumatol 32:4 747-751, 2005
    Organism: Departement de medecine de l'Enfant et de l'Adolescent, Service de Dermatologie, Centre Hospitalier Regional et Universitaire de Rennes, Rennes, France vhentgen@ch-versaillesfrFAU - Hentgen, Veronique
    Abstract: Among hereditary inflammatory disorders, Muckle-Wells syndrome, chronic infantile neurological cutaneous and articular syndrome (CINCA), and familial cold urticaria have recently been shown to be caused by dominantly inherited mutations in the CIAS1 gene. Reports suggest that these 3 diseases result from distinct missense mutations, with very few overlapping symptoms. We describe a French family presenting an intrafamilial overlapping clinical phenotype of CINCA and Muckle-Wells syndrome, caused by a mutation in CIAS1 gene. Clinical and genetic observations suggest that Muckle-Wells syndrome, CINCA, and familial cold urticaria are various phenotypic expressions of the same disease

16. HICK S, DEMERS PE, BRUNETTE I, LA C, MABON M, DUCHESNE B: Amniotic membrane transplantation and fibrin glue in the management of corneal ulcers and perforations: a review of 33 cases. Cornea 24:4 369-377, 2005
    Organism: Department of Ophthalmology, University of Liege, BelgiumFAU - Hick, Sandrine
    Abstract: PURPOSE: To evaluate the efficacy of amniotic membrane in corneal ulcers refractive to conventional treatment and amniotic membrane with fibrin glue in corneal perforations. METHODS: Amniotic membrane transplantation (AMT) was performed in 33 eyes from 32 patients for corneal ulcers refractive to conventional treatment. Fourteen ulcers were perforated and received fibrin glue and amniotic membrane. Ulcers were divided into 3 groups: neurotrophic or exposure, autoimmune, and other etiology. RESULTS: Overall success was observed in 80% (27/33 eyes) of the cases, with success rates of 87.5% (14/16 eyes), 70% (7/10 eyes), 85.7% (6/7 eyes) in groups 1, 2, and 3, respectively. The ulcers healed in a mean time of 3.6 +/- 1.6 weeks and the follow-up was 14.8 +/- 9.9 months. Failure was noted in 6 eyes with severe neurotrophic keratitis, Stevens-Johnson syndrome, ocular cicatricial pemphigoid, and Acanthamoeba keratitis. Grafts with fibrin sealant showed a success rate of 92.9 % (13/14 eyes) compared to 73.7% (14/19 eyes) for amniotic grafts alone. In patients with severe limbal damage, a success rate of only 20% (1/5) was observed. CONCLUSIONS: AMT is a viable option in the treatment of nonhealing corneal ulcers of various depth and etiologies. Perforations up to 3 mm can be safely managed by fibrin glue and AMT. These techniques lead to rapid reconstruction of the corneal surface and can give a good final functional result or allow keratoplasty to be done in more favorable conditions

17. HINKS A, BARTON A, JOHN S, BRUCE I, HAWKINS C, GRIFFITHS CEM, DONN R, THOMSON W, SILMAN A, WORTHINGTON J: Association between the PTPN22 gene and rheumatoid arthritis and juvenile idiopathic arthritis in a UK population: Further support that PTPN22 is an autoimmunity gene. Arthritis and Rheumatism (United States ) 52:6 1694-1699, 2005
    Abstract: Objective. The protein tyrosine phosphatase N22 (PTPN22) gene exhibits regulatory activities for both T cells and B cells. A missense single-nucleotide polymorphism (SNP) within this gene (rs2476601) has recently been associated with 4 autoimmune diseases: rheumatoid arthritis (RA), systemic lupus erythematosus, autoimmune thyroid disease, and type 1 diabetes mellitus, all of which are T cell-mediated and associated with the elaboration of autoantibody. The aim of this study was to investigate associations of the missense SNP of PTPN22 in a number of autoimmune diseases in the UK population, i ncluding RA, juvenile idiopathic arthritis (JIA), psoriasis, psoriatic arthritis (PsA), and multiple sclerosis (MS), some of which have not been examined previously. Methods. The PTPN22 missense SNP was genotyped in 886 RA, 661 JIA, 279 psoriasis, 455 PsA, and 379 MS patients and in 595 healthy controls. Association with the PTPN22 SNP was analyzed by chi-square test as implemented in Stata software. Results. There was a significant association between the PTPN22 SNP and RA (P = 1.8 x 10SUP-8 and JIA (P = 0.0005). In contrast, no association with psoriasis, PsA, or MS was detected. Conclusion. We replicated the findings of a previous association with RA and identified a novel association with JIA. Together with previous data showing associations with other autoimmune diseases, our Findings provide further evidence that the PTPN22 gene plays a role in the pathogenesis of a subgroup of autoimmune diseases. (c) 2005 American College of Rheumatology

18. HORNEFF G: Treatment of juvenile idiopathic arthritis
    STELLENWERT DER NEUEN BIOLOGICALS UND ZYTOKINANTAGONISTEN IN DER THERAPIE DER JUVENILEN IDIOPATHISCHEN ARTHRITIS (JIA). Zeitschrift fur Rheumatologie (Germany ) 64:5 317-326, 2005
    Abstract: Juvenile idiopathic arthritis is group of diseases of unknown aetiology characterised by the occurrence of chronic arthritis during childhood. Compared to adult onset rheumatoid arthritis, its course is more variable. Increasing knowledge of the inflammatory process as well as in molecular genetics and biotechnology has enable the production of new drugs, the biologicals. These are able to specifically block mechanisms of immune activation and thereby interfere with the inflammatory process. An increasing number of biol ogicals have been tried in clinical studies in adults suffering from rheumatoid arthritis, psoriasis or psoriasis arthritis and a couple of them were already licensed for treatment. Treatment of juvenile idiopathic arthritis by blockade of tumournecrosis-factor (TNF) using the soluble receptor Etanercept or the monoclonal antibodies Infliximab and Adalimumab showed comparable clinical efficacy. Blockade of TNF therefore already reached a certain place in the therapeutic algorythm for treatment of juvenile idiopathic arthritis. Currently, only Etanercept is licensed for treatment of active juve nile polyarthritis refractory to methotrexate. Studies using Infliximab and Adalimumab will be completed in the near future. However, antibodies blocking TNF may already be used in patients suffering from active uncontrolled chronic uveitis in whom visual impairment is threatening. TNF blockers may also be indicated in juvenile ankylosing spondylitis. The use of further biologicals, the interleukin-1 receptor antagonist Anakinra, Atlizumab (MRA) blocking the receptor for interleukin-6 or Abatacept, an inhibitory ligand of the co-stimulatory T cell membrane molecule CD28, remain experimental and should be preserved for clinical studies. (c) Steinkopff Verlag 2005

19. KAMPHUIS S, KUIS W, DE JAGER W, TEKLENBURG G, MASSA M, GORDON G, BOERHOF M, RIJKERS GT, UITERWAAL CS, OTTEN HG, SETTE A, ALBANI S, PRAKKEN BJ: Tolerogenic immune responses to novel T-cell epitopes from heat-shock protein 60 in juvenile idiopathic arthritis. Lancet 366:9479 50-56, 2005
    Organism: Department of Paediatric Immunology, IACOPO Institute for Translational Medicine, University Medical Centre Utrecht, Utrecht, The NetherlandsFAU - Kamphuis, Sylvia
    Abstract: BACKGROUND: Juvenile idiopathic arthritis is a heterogeneous autoimmune disease characterised by chronic inflammation of one or more joints. In patients with this disease, T-cell reactivity to autologous heat-shock protein 60 (HSP60) is associated with a favourable prognosis. We sought to identify HSP60 T-cell epitopes to find potential targets for HSP60 immunotherapy and to assess whether immune responses to these epitopes contribute to the distinct clinical outcome of this disease. METHODS: We identified eight potential epitopes using a computer algorithm from both self and microbial HSP60 binding to many HLA-DR molecules. We analysed the pattern of T-cell responses induced by these HSP60 peptides in peripheral-blood mononuclear cells (PBMC) of 57 patients with juvenile idiopathic arthritis, 27 healthy controls, and 20 disease controls. We undertook in-vitro MHC binding studies with the identified peptides, and HLA class II typing of a subset of patients with juvenile idiopathic arthritis. FINDINGS: Five of the eight peptides identified yielded proliferative T-cell responses in 50-70% of PBMC from patients with juvenile idiopathic arthritis irrespective of MHC genotype, but not in PBMC from healthy or disease controls. Although PBMC from both patients with juvenile idiopathic arthritis and healthy controls produced interferon gamma in response to these peptides, only PBMC from patients with the disease produced interleukin 10. INTERPRETATION: The recorded T-cell-induction in juvenile idiopathic arthritis is tolerogenic. In patients with oligoarticular disease, the immune responses to the HSP60 epitopes identified could contribute to disease remission. RELEVANCE TO PRACTICE: The broad recognition of these HSP60 epitopes in a population of patients with polymorphic MHC genotypes opens the way for HSP60-peptide immunotherapy, representing a novel treatment option to specifically modulate the immune system in patients with juvenile idiopathic arthritis

20. KINGSLEY GH, KHOSHABA B, SMITH CM, CHOY EH, SCOTT DL: Are clinical trials in rheumatoid arthritis generalizable to routine practice? A re-evaluation of trial entry criteria. Rheumatology (Oxford) 44:5 629-632, 2005
    Organism: Department of Rheumatology, GKT School of Medicine, Weston Education Centre, Kings College, Cutcombe Road, London SE5, UK gabriellekingsley@kclacukFAU - Kingsley, G H
    Abstract: OBJECTIVE: Trials of disease-modifying anti-rheumatic drugs (DMARDs) enrol active rheumatoid arthritis patients identified using standard criteria (three out of four of: >/=6 tender joints, >/=6 swollen joints, ESR >/= 28 mm/h, >/=45 min morning stiffness). Concern has been expressed about generalizability, as many patients in routine practice have less active disease. Furthermore, these criteria do not map onto standard disease activity and treatment response measures. We examined how many routine patients were sufficiently active to meet trial recruitment criteria and whether alternative definitions of active disease were more appropriate. METHODS: We studied 504 patients in a cross-sectional study, 156 in a longitudinal study and 94 starting new DMARDs or biologics. Patients were classified as 'trial active' (met entry criteria), in remission or 'intermediately active' (between the two). We also evaluated the effect of amendments to criteria. RESULTS: Cross-sectionally only 38% patients were 'trial active', but longitudinally 68% were 'trial active' at least once. Thus, many clinic patients do have disease activity below the level required for trial entry, but over time most reach eligibility levels. More (62%) of the cohort starting new treatment were 'trial active', suggesting that recruitment criteria relate to clinical decisions. Criteria omitting morning stiffness and a disease activity score (DAS28) >/=5.4 replicated the classification given by current criteria. CONCLUSIONS: Trial results can be generalized to routine practice because most clinic patients are 'trial active' when their therapy is changed and most become 'trial active' over time. As DAS-based criteria are simpler and relate directly to response measures, their use should be considered in future

21. LAUKENS D, PEETERS H, MARICHAL D, VANDER CB, MIELANTS H, ELEWAUT D, DEMETTER P, CUVELIER C, VAN DEN BM, ROTTIERS P, VEYS EM, REMAUT E, STEIDLER L, DE KEYSER F, DE VOS M: CARD15 gene polymorphisms in patients with spondyloarthropathies identify a specific phenotype previously related to Crohn's disease. Ann Rheum Dis 64:6 930-935, 2005
    Organism: Department of Gastroenterology, Ghent University Hospital, De Pintelaan 185, B-9000 Ghent, BelgiumFAU - Laukens, D
    Abstract: BACKGROUND: The association between spondyloarthropathy and Crohn's disease is well known. A risk for evolution to Crohn's disease has already been shown in the subgroup of patients with spondyloarthropathy associated with chronic gut inflammation. OBJECTIVE: To investigate whether the reported polymorphisms in the CARD15 gene, a susceptibility gene for Crohn's disease, are associated with the presence of preclinical intestinal inflammation observed in spondyloarthropathies. METHODS: 104 patients with spondyloarthropathies were studied. All underwent ileocolonoscopy with biopsies between 1983 and 2004. The prevalence of three single nucleotide polymorphisms in the CARD15 gene (R702W, G908R, and 1007fs) was assessed using restriction fragment length polymorphism-polymerase chain reaction (RFLP-PCR); the patients were compared with an ethnically matched Crohn's disease population and a control population. RESULTS: The carrier frequency of R702W, G908R, or 1007fs variants in the spondyloarthropathy populations (20%) was similar to the control population (17%), but increased to 38% in the spondyloarthropathy subgroup with chronic gut inflammation. This frequency was significantly higher than in the other spondyloarthropathy subgroups (p = 0.001) or the control group (p = 0.006), but not different from the Crohn's disease group (49%) (NS). This indicates that CARD15 polymorphisms are associated with a higher risk for development of chronic gut inflammation. CONCLUSIONS: CARD15 gene polymorphisms clearly identify a subgroup of patients with spondyloarthropathies associated with chronic intestinal inflammation

22. LEHMAN TJ: Juvenile idiopathic arthritis and HSP60 vaccination: selective down-regulation? Lancet 366:9479 9-10, 2005
    Organism: Division of Pediatric Rheumatology, Hospital for Special Surgery, Weill Medical College of Cornell University, New York, NY 10021, USA goldscout@aolcomFAU - Lehman, Thomas J A

23. LIANG TC, HSU CT, YANG YH, LIN YT, CHIANG BL: Analysis of childhood reactive arthritis and comparison with juvenile idiopathic arthritis. Clin Rheumatol 24:4 388-393, 2005
    Organism: Department of Pediatrics, National Taiwan University Hospital, No 7 Chung-Shan South Road, Taipei, Taiwan, Republic of China, gicmbor@hamcntuedutwFAU - Liang, Tien-Chi
    Abstract: There is currently no agreement on how to classify and diagnose reactive arthritis (ReA) and what kind of clinical and laboratory findings are specific for the diagnosis. This study retrospectively analyzed the initial clinical manifestations and laboratory findings in children diagnosed with ReA and juvenile idiopathic arthritis (JIA). A comparison was also made between these two groups to see if there were differences. A retrospective chart review was performed and 44 patients diagnosed with ReA and 80 patients with JIA were enrolled in this study. Their initial clinical manifestations and laboratory findings were also analyzed and compared. The initial clinical manifestations in ReA were analyzed including the demographic data, the preceding infection history, the duration of the infectious episode to the onset of arthritis, the duration of arthritic symptoms, and the involved joint pattern. Comparison of the initial laboratory findings between patients with ReA and JIA showed significant differences between erythrocyte sedimentation rates (ESR) in the first hour, platelet counts (p<0.05), and ESR in the second hour (p=0.052). Further, comparing ReA with the subtypes of JIA, significant differences were noted between ReA and the systemic type in terms of hemoglobin level, platelet counts, C-reactive protein, and first and second hour ESR (p<0.05). However, if compared with the polyarticular or pauciarticular type, only the platelet counts showed any significant statistical difference (p<0.05). This study summarizes clinical experiences in ReA. The differences in laboratory findings of ReA and JIA may provide a clue in making a differential diagnosis

24. LIEN G, SELVAAG AM, FLATO B, HAUGEN M, VINJE O, SORSKAAR D, DALE K, EGELAND T, FORRE O: Bone mass changes and bone turnover in children with early juvenile idiopathic arthritis and healthy controls. J Bone Miner Res 19: S189, /10/4

25. LUNDQVIST A, ISA A, TOLFVENSTAM T, KVIST G, BROLIDEN K: High frequency of parvovirus B19 DNA in bone marrow samples from rheumatic patients. J Clin Virol 33:1 71-74, 2005
    Organism: Clinic of Infectious Diseases, Sodra Alvsborg Hospital, S-50182 Boras, SwedenFAU - Lundqvist, Anders
    Abstract: BACKGROUND: Human parvovirus B19 (B19) polymerase chain reaction (PCR) is now a routine analysis and serves as a diagnostic marker as well as a complement or alternative to B19 serology. The clinical significance of a positive B19 DNA finding is however dependent on the type of tissue or body fluid analysed and of the immune status of the patient. OBJECTIVES: To analyse the clinical significance of B19 DNA positivity in bone marrow samples from rheumatic patients. STUDY DESIGN: Parvovirus B19 DNA was analysed in paired bone marrow and serum samples by nested PCR technique. Serum was also analysed for B19-specific IgG and IgM antibodies and the results were compared with clinical and epidemiological data. RESULTS AND CONCLUSIONS: B19 IgG was found in 41 of 50 patients (82%) whereas none was B19 IgM positive. The serologic evaluation showed that none of the patients had acute B19 infection. However, B19 DNA was detected by PCR in 13 of 50 (26%) bone marrow samples from these patients indicating a high frequency of persistent infection compared with previous reports of patient groups and healthy controls. In the study, 22 patients had rheumatoid arthritis (RA) and 7 of these RA patients were B19 DNA positive in bone marrow. Rheumatoid factor was positive in 4 of the 7 B19 DNA positive RA patients as compared with Rheumatoid factor positivity in all of the 15 B19 DNA negative RA patients. Erosive arthritis in X-ray was less common in the B19 DNA positive group than in the B19 DNA negative group. A high frequency of parvovirus B19 DNA was thus detected in bone marrow samples in rheumatic patients. The clinical data does not support a direct association between B19 PCR positivity and rheumatic disease manifestation. Therefore, the clinical significance of B19 DNA positivity in bone marrow samples from rheumatic patients must be interpreted with caution

26. MATEICKA F, BLAZICKOYA S, ROVENSKY P, KRCMERY V: Autologous stem cell transplantation in patient with juvenile idiopathic arthritis. I. Clinical course of the disease. International Journal of Antimicrobial Agents 24: S172-S173, /12/4

27. MEKAN SF, SAEED O, KHAN JA: Invasive aspergillosis with polyarthritis. Mycoses 47:11-12 518-520, 2004
    Organism: Department of Biological and Biomedical Sciences, The Aga Khan University Hospital, Karachi, Pakistan sabeenmekan@hotmailcomFAU - Mekan, S F
    Abstract: We report a case of septic arthritis of multiple joints in an 18-year-old male caused by Aspergillus fumigatus. His initial presentation was of low-grade fever followed by involvement of both knee and ankle joints. Later, there was also involvement of metacarpophalangeal joints. Diagnosis was based on biopsy and culture of the skin and joint lesions. The symptoms resolved readily under administration of itraconazole. We recommend that clinicians should be alerted of potential fungal etiology in cases of fever and chronic arthritis, which is unresponsive to conventional medical therapy

28. MESIHOVIC-DINAREVIC S, IBRAHIMOVIC J: Up-to-date approach to treatment of juvenile rheumatoid arthritis. Med Arh 59:3 196-198, 2005
    Organism: Pedijatrijska klinika, Klinicki centar Univerziteta u SarajevuFAU - Mesihovic-Dinarevic, Senka
    Abstract: PURPOSE: Juvenile rheumatoid arthritis (JRA) is the most common form of arthritis in paediatric population. The aim of this study is to evaluate patients (pts) with JRA in correlation to age, sex, type of illness as well as treatment algorhytm and its efficacy. WORK METHOD: During period time from 1.1.2002. till 31.12.2001. patients with JRA hospitalised at Paediatric Clinic of the Clinical Centre of University of Sarajevo were retrospectively studied. The soruce of research was histories of illness, clinical examinations and clinical findings during follow-up period. WORK RESULTS: according to our data girls were more often affected with JRA-23 patients (66%) age 2 to 6 years. The most frequent type of illness was monoarticular in 48.5%, polyarticular 34.2% and systemic in 14.3%. All pts were treated with first line therapy: nonsteroid anti-inflammatory agents combined with physio therapy which had satisfactory outcome, so 80% patients entered the remission zone of illness. Patients with systemic (14.3%) and polyarticular form with complications, received steroid therapy. One patient with systemic form was treated withmethotrexat. Duration of pts stay at Clinic differ from illness, 35% were cured and 5% non-cured patients. DISSCUSION: Treatment of JRA is a combination of medications, physio therapy and psycho therapy. The goals of treatment are to relive pain and inflammation, slow down or to prevent the destruction of joints and to restore use and function of affected joints in order to promote optimal child's growth and development, physicalactivity, social and emotional development. CONCLUSION: Treatment with nonsteroid antireumatics in combination with physio therapy proved very successful in patents with JRA. Multidisciplinary approach is mandatory to achieve primary goal: to cure illness. It is necessary to start therapeutic algorhytm as early as possible in best patient's interest

29. MICHELS H: Juvenile idiopathic arthritis - When do we need glucocorticoids?
    JUVENILE IDIOPATHISCHE ARTHRITIS - WANN BRAUCHEN WIR GLUCOCORTICOIDE? Aktuelle Rheumatologie (Germany ) 30:3 183-186, 2005
    Abstract: Glucocorticoids are still an essential part of the treatment of juvenile idiopathic arthritis (JIA). They can be given locally or systemically. Indications for the local therapy are rheumatic uveitis and florid arthritis. In JIA, the use of systemic glucocorticoids is mainly limited to treating severe extra-articular features, such as severe myo-/pericarditis, rheumatic vasculitis, septic fever in systemic-onset disease, cystic macula edema associated with uveitis, and macrophage activation syndrome (MAS). The i.v. pulse therapy is reserved for emergency situations, such as MAS and acute intervention of severe courses of disease, and especially for the initiation of the treatment of uveitis with acute synechiae and for bridging therapy until disease modifying drugs (DMARDs) take effect. The preferred drugs are still prednisone/prednisolone, for pulse therapy methylprednisolone. Long lasting treatments with doses > 0.2 mg prednisolone/kg bw/day should be restricted to severe courses of the disease. All opportunities to minimize adverse effects, such as additional treatment with DMARDs and the use of biologicals or alternate-day dosage should be tried. Systemic glucocorticoids should only cautiously be given as anti-arthritic therapy. In any case, an anti-arthritic therapy does not justify a reduction of the patient's growth velocity. (c) Georg Thieme Verlag KG Stuttgart

30. MICHELS H: The spectrum of rheumatic diseases in adolescence
    SPEKTRUM RHEUMATISCHER ERKRANKUNGEN BEI JUGENDLICHEN. Aktuelle Rheumatologie (Germany ) 30:3 153-156, 2005
    Abstract: Numerous rheumatic diseases may persist from early childhood into adolescence, while other rheumatic disorders may appear in adolescence for the first time. The main categories are juvenile idiopathic arthritis (JIA), the connective tissue diseases, and systemic vasculitides. Other examples are the pain-amplifying syndromes or the periodic fever syndromes. Long-lasting rheumatic disorders persisting into adolescence may end up in irreversible damage of the joints or, as a result of uveitis, the eyes, or may lead to amyloid A amyloidosis. These problems affect young persons who are going through a time of upheaval by finding his or her bearings at school or taking up his or her career. All this at a time when the parents retire from their supervision. (c) Georg Thieme Verlag KG Stuttgart

31. MILLER V, MICHELS H: Complementary and alternative medicine in pediatric rheumatology
    KOMPLEMENTARE THERAPIEN IN DER KINDERRHEUMATOLOGIE. Aktuelle Rheumatologie (Germany ) 30:3 195-198, 2005
    Abstract: Complementary and alternative therapies (CAM) are very popular in pediatric rheumatology patients. This article reviews popular therapies like diet suggestions, fish oil, long chain vegetable oil, vitamin supplementation, phytotherapy, and acupuncture. (c) Georg Thieme Verlag KG Stuttgart

32. MINDEN K, NIEWERTH M: Children turn into adolescents - Management problems
    AUS "KIDS" WERDEN "TEENS" - PROBLEME IM MANAGEMENT. Aktuelle Rheumatologie (Germany ) 30:3 157-161, 2005
    Abstract: Adolescents have numerous developmental milestones to achieve. A chronic rheumatic disease may have major effects upon the adolescents' bio-psychosocial development. Growth and bone mineralization may be affected by a rheumatic disease, as well as the development of social competence and emancipation from parents with emotional and financial independence. On the other hand, risky behavior common in adolescence may influence the prognosis of the rheumatic disease. Therefore, not only disease-specific but also developmental and generic health issues have to be addressed in transitional care. The provision of high quality, coordinated, uninterrupted health care that is patient-centered and developmentally appropriate is important for a successful transition into adulthood. (c) Georg Thieme Verlag KG Stuttgart

33. MINDEN K, NIEWERTH M, ZINK A, GANSER G: Transition clinic - Bridging the gap between paediatric and adult care
    TRANSITION-CLINIC - DER NICHT IMMER EINFACHE UBERGANG IN DIE RHEUMATOLOGIE FUR ERWACHSENE. Zeitschrift fur Rheumatologie (Germany ) 64:5 327-333, 2005
    Abstract: Chronic inflammatory rheumatic diseases with onset in childhood often persist into adulthood and result in a considerable number of patients in impairments of body functions and structures, activities at the individual level and participation in society. Continuation of health care beyond adolescence is, therefore, necessary. Its provision should be of high quality, coordinated, uninterrupted, patient-centred and developmentally appropriate to ensure smooth transitions between children's and adult services and positive outcomes of transition for the young people themselves. Existing research is very persuasive on the need to improve transitions for young people with rheumatic diseases. To achieve effective transition, not only disease specific, but also aspects of growth and development have to be taken into accou nt. Paediatric and adult rheumatologists should establish close cooperations and implement specific transition programs to meet the special health care needs of these patients. (c) Steinkopff Verlag 2005

34. MUELLER-GODEFFROY E, LEHMANN H, KUESTER RM, THYEN U: Quality of life and psychosocial adaptation in children and adolescents with juvenile idiopathic arthritis and reactive arthritis
    <ORIGINAL> Lebensqualitat und psychosoziale Anpassung bei Kindern und Jugendlichen mit juveniler idiopathischer Arthritis und reaktiven Arthritiden. Zeitschrift fuer Rheumatologie 64:3 177-187, /4/5
    Abstract: Objective We sought to measure self-reported health related quality of life (HRQOL) and psychosocial adaptation in children and adolescents with juvenile idiopathic arthritis (JIA) and reactive arthritis and to determine factors associated with these outcomes. Methods We interviewed 72 children and adolescents with chronic arthritis, age 8-16, about HRQOL (KINDL-R-Questionnaire) and functional ability in activities of daily living (Childhood Health Assessment Questionnaire - CHAQ). Mothers reported behavior problems (Child Behavior Checklist - CBCL). Results Children and adolescents with juvenile idiopathic arthritis and reactive arthritis reported lower HRQOL compared to normative data in several areas. Children reported lower QOL in the d imensions self-esteem; adolescents reported lower QOL in the dimensions physical well being and total QOL. Almost 20% of the sample appeared to have serious behavior problems, mostly social isolation and depression/anxiety. Functional limitations affected HRQOL and behavior problems. Inpatient children and adolescents and those with shorter disease duration reported lower QOL than outpatient children and adolescents and those with longer disease duration. Best predictors for impaired HRQOL were functional limitations, social isolation and depression/anxiety. Conclusions Self-reported HRQOL and behavior problems may be relevant outcome measures in children and adolescents with chronic arthritis and useful to monitor psychosocial support in this population

35. MYER GD, BRUNNER HI, MELSON PG, PATERNO MV, FORD KR, HEWETT TE: Specialized neuromuscular training to improve neuromuscular function and biomechanics in a patient with quiescent juvenile rheumatoid arthritis. Phys Ther 85:8 791-802, 2005
    Organism: Sports Medicine Biodynamics Center and Human Performance Laboratory, Cincinnati Children's Hospital Medical Center, 3333 Burnet Ave, MLC 10001, Cincinnati, OH 45229, USA gregmyer@cchmcorgFAU - Myer, Gregory D
    Abstract: BACKGROUND AND PURPOSE: The purpose of this case report is to describe a novel multidisciplinary approach for evaluating and preparing a patient with quiescent juvenile rheumatoid arthritis (JRA) for safe sports participation. CASE DESCRIPTION: The patient was a 10-year-old girl with a history of bilateral knee arthritis who desired to participate in soccer and basketball. Range of motion and manual muscle testing of the lower extremity were within normal limits. Neuromuscular testing included kinematic and kinetic testing, isokinetic assessment, and postural stability testing. The patient's gait was near normal; however, she had narrowed step width and increased knee flexion at heel-strike. Landing analysis during a box drop vertical jump task showed increased and imbalanced (right versus left lower extremity) peak impact forces. The testing was followed by specialized neuromuscular training (SNT). OUTCOMES: Following SNT, heel-strike and step width were within normal limits, peak impact forces on the box drop test decreased by 31%, imbalance decreased by 46%, and vertical jump increased 15%. The isokinetic strength ratio between knee flexors and extensors and the overall balance measures were within normal limits and equal bilaterally. DISCUSSION: Patients with quiescent JRA may have abnormal biomechanics, which could place them at increased risk for injury or future articular cartilage damage. Specialized neuromuscular training may have helped to decrease the patient's risk for future injury or disease progression

36. ODENT T, JOURNEAU P, PRIEUR A-M, TOUZET P, POULIQUEN J-C, GLORION C: Cementless hip arthroplasty in juvenile idiopathic arthritis. Journal of Pediatric Orthopaedics (United States ) 25:4 465-470, 2005
    Abstract: Juvenile idiopathic arthritis (JIA) is the most common rheumatic disease in children. The hip is usually affected later, and its involvement is the most common cause of disability in JIA. Failure of medical and preventive treatment, significant joint destruction, or multiarticular involvement may necessitate total hip arthroplasty (THA) to restore good function. Related clinical trials show initially good THA results in most of the series, but long-term outcomes are uncertain due to a significant arthroplasty loosening rate in the initial years, particularly with cemented stems. The authors report the results of 62 noncemented THAs in 34 children with JIA after an av erage follow-up of 6 years (range 3-13). Mean age at surgery was 18.3 years (range 11.8-31) and 14 of the 34 children had active disease. Clinical results were good for hip function but less for global function. There were no infections. Two acetabular cups early in the series failed due to poor primary fixation and had to be revised. Survivorship analysis was performed with the Kaplan-Meier method. At 13 years, the survival rate was 100% for the femoral component and 90.1% for the acetabular component. Copyright (c) 2005 by Lippincott Williams & Wilkins

37. OEN K, ROBINSON DB, NICKERSON P, KATZ SJ, CHEANG M, PESCHKEN CA, CANVIN JMG, HITCHON CA, SCHROEDER M-L, EL GABALAWY HS: Familial seropositive rheumatoid arthritis in North American native families: Effects of shared epitope and cytokine genotypes. Journal of Rheumatology (Canada ) 32:6 983-991, 2005
    Abstract: Objective. A number of North American native (NAN) populations have high prevalence rates of both rheumatoid arthritis (RA) and the shared epitope (SE). We examined the phenotype and familial incidence of RA in a NAN population, and investigated how the SE and cytokine genes may affect disease risk within affected families. Methods. NAN patients with seropositive RA or polyarthritis rheumatoid factor (RF) positive juvenile idiopathic arthritis (JIA) were identified from clinical databases. Patients were recruited consecutively as they presented for clinic visits. Family pedigrees were constructed and consenting relatives were interviewed and examined. The risk of RA within families was calculated by multiple logistic regression. Input variables were the SE and cytokine genotypes. Probands and affected relatives were entered as the affected group, and unaffected relatives within families as the unaffected group. Results were confirmed among unrelated subjects, i.e., unrelated patients and unaffected relatives of other probands. Results. The familial prevalence of RA was 0.50 (95% confidence intervals 0.30, 0.70) among 28 families studied. The interleukin 10 (IL-10) promoter -1082G/A genotype decreased the odds of RA relative to the A/A genotype in affected families (OR 0.247, 95% CI 0.081, 0.751; p = 0.014) and among unrelated subjects (OR 0.203, 95% CI 0.064, 0.640; p = 0.006). The G/G genotype yielded an OR of 0.093 (95% 0.013, 0.676; p = 0.019) among unrelated subjects. The SE had no effect in these calculations. Conclusion. There was a high familial prevalence of RA in this NAN cohort. In susceptible NAN families, the risk of RA was reduced by IL-10 genotypes, whereas the SE did not affect risk. Study of healthy NAN controls is required to determine if these conclusions apply to this NAN population as a whole

38. OFFIAH AC, WOO P, PRIEUR AM, HASSON N, HALL CM: Camptodactyly-arthropathy-coxa vara-pericarditis syndrome versus juvenile idiopathic arthropathy. AJR Am J Roentgenol 185:2 522-529, 2005
    Organism: Department of Radiology, Great Ormond Street Hospital for Children, Great Ormond St, London WC1N 3JH, UKFAU - Offiah, Amaka C
    Abstract: OBJECTIVE: The objective of our article was to highlight the important clinical and radiographic features of camptodactyly-arthropathy-coxa vara-pericarditis (CACP) syndrome. In particular, we emphasize those features that allow differentiation of CACP syndrome from juvenile idiopathic arthropathy. CONCLUSION: CACP syndrome should be considered in all patients who present with a noninflammatory arthropathy or with "atypical juvenile idiopathic arthritis," particularly if radiographs reveal an absence of erosions. In the correct clinical setting, large acetabular cysts on pelvic radiographs may be considered pathognomonic of CACP syndrome

39. OKAMOTO Y, NISHIDA M: Dual-color ELISPOT assay for analyzing cytokine balance. Methods Mol Biol 302:263-72.: 263-272, 2005
    Organism: Division of Health Care Pharmacy, Faculty of Pharmacy, Meijo University, Tempaku-ku, Nagoya, Aichi, JapanFAU - Okamoto, Yoshihiro
    Abstract: A dual-color enzyme-linked immunospot (ELISPOT) assay enabled us to analyze three kinds of cytokine-secreting cells simultaneously. T helper (Th) cells can be subdivided into at least two distinct functional subsets based on their cytokine secretion profiles. The first type of clones (Th1) produces interleukin (IL)-2 and interferon (IFN)-gamma but not IL-4 or IL-5. The second type of clones (Th2) produces IL-4 and IL-5 but not IL-2 or IFN-gamma. Furthermore, the presence of the third type (Th0) cell, which is a precursor of Th1 or Th2 cells, has been demonstrated to produce both Th1- and Th2-type cytokines. The dual-color ELISPOT assay is developed to differentiate these three subtypes of Th cells in an identical well. In the system, the red spots corresponding to IL-2-secreting cells (Th1) were developed with horseradish peroxidase and amino-ethyl-carbazole/H2O2. The light blue spots corresponding to IL-4-secreting cells (Th2) were developed with alkaline phosphatase and Vector blue (chromogenic substrate for alkaline phosphatase). The mixed colored (indigo) spots corresponding to both kinds of cytokine-secreting cells (Th0 cells) were developed with both chromogenic substrates. With this system, we could detect the IL-2- and/or IL-4-secreting cells simultaneously in a murine spleen cell or human peripheral mononuclear cell preparation

40. OSTENSEN M: Problems of adolescence: Sexuality and reproduction in patients with juvenile idiopathic arthritis
    PROBLEME IN DER ADOLESZENZ: SEXUALITAT UND REPRODUKTION BEI PATIENTEN MIT JUVENILER IDIOPATHISCHER ARTHRITIS (JIA). Aktuelle Rheumatologie (Germany ) 30:3 162-167, 2005
    Abstract: Sexual dysfunction can arise in female and male patients with JIA and is most often related to pain, fatigue, and physical impairment as well as to reduced self esteem. Antirheumatic drugs can interfere with fertility because of gonadotoxicity. The role of NSAID in delaying ovulation has not been sufficiently clarified. Gonadotoxic effects of immunosuppressive drugs depend on their mechanism of action, dose and duration of treatment. Alkylating agents can induce amenorrhea in women, and oligo- or azoospermia in men, but recovery of the gonadal function is possible. Preservation of fertility during cyclophosphamide therapy can be achieved by gonadotropin releasing hor mone (GnRH) agonists in women and by sperm banking before commencement of the therapy in men. Pregnancy does not reactivate a JIA in remission, but a flare occurs in 58% of women with JIA post partum regardless of disease activity at conception. The polyarticular and oligoarticular forms of JIA benefit mostly from pregnancy whereas the systemic form does not. As a rule, JIA does not impair fetal outcome. Drug treatment during pregnancy may be necessary in women with active JIA. The classic non-selective nonsteroidal anti-inflammatory drugs are not teratogenic, but given in late pregnancy they can induce renal and cardiac side effects in the fetus. NSAID should therefore be stopped by gestational week 32. Corticosteroids are frequently neces sary to control rheumatic disease flares, but high doses (1-2 mg/kg) should be avoided in the first trimester because of an increased risk of oral clefts. Among disease modifying drugs, sulfasalazine and antimalarials have the safest record. Cyclosporine and azathioprine can be given throughout pregnancy if disease control requires it. Insufficient data exist for treatment of pregnant patients with TNF-inhibitors. Prophylactic withdrawal of drugs before pregnancy is mandatory for the cytotoxic agents methotrexate and cyclophosphamide. Previous treatment with cytotoxic drugs does not imply negative effects on future offspring of patients with JIA. (c) Georg Thieme Ver lag KG Stuttgart

41. PALMER DH, MULHALL KJ, THOMPSON CA, SEVERSON EP, SANTOS ER, SALEH KJ: Total knee arthroplasty in juvenile rheumatoid arthritis. J Bone Joint Surg Am 87:7 1510-1514, 2005
    Organism: St Croix Orthopaedics, 1701 Curve Crest Boulevard, Stillwater, MN 55082FAU - Palmer, David H
    Abstract: BACKGROUND: There is a paucity of reports regarding the long-term results of total knee arthroplasty in patients with juvenile rheumatoid arthritis. The purpose of this study was to evaluate the outcome of total knee arthroplasty in patients with juvenile rheumatoid arthritis who had been followed for a minimum of twelve years. METHODS: Eight consecutive patients (fifteen knees) with juvenile rheumatoid arthritis underwent total knee arthroplasty at an average age of 16.8 years. Clinical evaluation of pain status, range of motion, and the ability to walk and radiographic evaluation of the alignment of the knees and component loosening were performed preoperatively and at a mean of 15.5 years postoperatively. RESULTS: All patients had substantial pain and functional limitation before the surgery, and seven of the eight patients used a wheelchair. At the time of the latest follow-up, which was after revision surgery in three patients, all of the knees were pain-free and six patients were able to walk about the community. The mean arc of motion had increased from 36 degrees to 79 degrees . The final radiographic evaluation showed that thirteen of the fifteen knees were in neutral alignment and two were in valgus. Failure, defined as revision of any of the components or definite loosening as seen radiographically, occurred in three knees. CONCLUSIONS: Good results, in terms of pain relief and restoration of function, were seen at a minimum of twelve years following total knee arthroplasty in our series of patients with juvenile rheumatoid arthritis. This procedure is a reasonable option when nonoperative therapy has been inadequate for patients with severe disability and pain in this relatively young population. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions to Authors for a complete description of levels of evidence

42. PEAKE NJ, KHAWAJA K, MYERS A, JONES D, CAWSTON TE, ROWAN AD, FOSTER HE: Levels of matrix metalloproteinase (MMP)-1 in paired sera and synovial fluids of juvenile idiopathic arthritis patients: relationship to inflammatory activity, MMP-3 and tissue inhibitor of metalloproteinases-1 in a longitudinal study. Rheumatology (Oxford) .: 2005
    Organism: Musculoskeletal Research Group, School of Clinical Medical Sciences, University of Newcastle-upon-Tyne, Newcastle-upon-Tyne, UK
    Abstract: Objectives. To measure levels of the collagenases matrix metalloproteinase (MMP)-1 and -13 in the synovial fluid (SF) and serum of patients with juvenile idiopathic arthritis (JIA), and to correlate these measurements with inflammatory activity, levels of the collagenase activator MMP-3 and the tissue inhibitor of metalloproteinases-1 (TIMP-1). Methods. Levels of MMP-1, -3, -13 and TIMP-1 were measured in paired SF and serum from 82 JIA patients using enzyme-linked immunsorbent assay and compared between subtypes and patients of different ages and disease durations. These levels were also correlated to the active joint count (AJC) and standard measures of inflammatory activity and therapeutic response, including erythrocyte sedimentation rate (ESR) and platelet count (PLT). Results. MMP-1 was detected in JIA SF and correlated with PLT. MMP-3 levels were high in SF and detectable in serum where they correlated with PLT, ESR and AJC. MMP-13, however, was not detected in SF or serum. No differences were observed between patients grouped by subtype, age or disease duration. MMP-3 contributed the majority of total MMP in SF samples resulting in excess MMP levels over TIMP-1. Conclusions. MMP-1 is up-regulated in SF concordant with inflammatory activity in JIA. This was true for patients in all JIA subtypes and age groups, suggesting that the capability for degradation of type II collagen is present in early disease, and throughout the disease course. MMP-3 may be important in the activation of collagenases and the saturation of exogenous inhibitors. Serum MMP-3 may therefore be a useful, measurable and specific marker of active disease in JIA

43. PUTOVA I, CIMBUROVA M, JAROSOVA K, VENCOVSKY J, HORAK J: Mutations in the HFE gene in patients with rheumatic diseases. Cas Lek Cesk 144:6 391-397, 2005
    Organism: Centrum biomedicinskych oboru - oddeleni bunecne a molekularni biologie 3 LF UK, Praha puto@revmaczFAU - Putova, I
    Abstract: BACKGROUND: Hereditary hemochromatosis is one of the most common autosomal recessive diseases. Aim of the study. 1. To establish frequency of C282Y and H63D mutations in the HFE gene (the hemochromatosis gene) in general population of the Czech Republic and in patients with hemochromatosis. 2. To find out whether hemochromatosis in homo- or heterozygous state plays a role in the pathogenesis of rheumatic diseases. METHODS AND RESULTS: In 32 patients with hereditary hemochromatosis, in 84 patients with polymyositis or dermatomyositis, in 246 patients with juvenile idiopathic arthritis and in 481 persons of the control group the presence of HFE gene mutations was etablished. The HFE gene mutations were screened for by restriction enzyme analysis performed on PCR amplified products. In the control group, 6.86% carriers of the C282Y mutation and 26.61% those of H63D were found. Homozygous C282Y or H63D mutation was found in 90.6% (p<0.001) of patients with hemochromatosis. Heterozygous C282Y mutation was found in 12.2% (p<0.05) of patients with juvenile idiopathic arthritis. We didn't detected higher prevalence of HFE gene mutations in patients with polymyositis and dermatomyositis. CONCLUSIONS: Results of this study show that heterozygosity for C282Y mutation may be a risk factor for juvenile idiopathic arthritis but not for polymyositis and dermatomyositis

44. ROBERTS S, EVANS H, MENAGE J, URBAN JP, BAYLISS MT, EISENSTEIN SM, RUGG MS, MILNER CM, GRIFFIN S, DAY AJ: TNFalpha-stimulated gene product (TSG-6) and its binding protein, IalphaI, in the human intervertebral disc: new molecules for the disc. Eur Spine J 14:1 36-42, 2005
    Organism: Centre for Spinal Studies, Robert Jones and Agnes Hunt Orthopaedic Hospital and Keele University, Oswestry, Shropshire, SY10 7AG, UK sroberts@keeleacukFAU - Roberts, Sally
    Abstract: Inflammation and irritation of the nerve roots has been indicated as an important factor in the pain associated with symptomatic disc herniations. Tumour necrosis factor alpha (TNFalpha) is now believed to be involved in this pathway. TNFalpha causes connective tissue cells in culture to synthesise a glycoprotein, TNFalpha-stimulated gene-6 (TSG-6). TSG-6 is found in inflammatory diseases of related connective tissues, such as articular cartilage in rheumatoid arthritis, but is not present in unaffected individuals. In order to determine if TSG-6 occurred in intervertebral disc (and cartilage endplate), we have investigated the presence of TSG-6 and its binding protein, inter-alpha-inhibitor (IalphaI), in 58 herniated and 15 non-herniated discs. Immunostaining for the cytokines, IL-1alpha, IL-1beta and TNFalpha, has also been carried out. We have demonstrated that both TSG-6 and IalphaI occur commonly in human intervertebral disc matrix with at least some TSG-6 in 98% of discs studied and IalphaI in all of them. Staining for TSG-6 was greatest in herniated discs, particularly close to blood vessels. IalphaI immunostaining was frequently widespread throughout the disc but there was little in the cartilage endplate. It has been proposed that these molecules have widespread effects, including extracellular matrix stabilisation, down-regulation of the protease network and reduction of inflammation. Hence, the occurrence of TSG-6 and IalphaI in disc tissue could have implications in the aetiopathogenesis and future therapeutics of intervertebral disc disease

45. ROBERTSON LP, MCDONAGH JE, SOUTHWOOD TR, SHAW KL: Growing up and moving on. A multicentre UK audit of the transfer of adolescents with Juvenile Idiopathic Arthritis JIA from paediatric to adult centred care. Ann Rheum Dis .: 2005
    Organism: Bristol Royal Infirmary, United Kingdom
    Abstract: OBJECTIVES: To assess the provisions made for the transfer of adolescents with juvenile idiopathic arthritis (JIA) to adult rheumatology clinics in the UK and the impact of a transitional care programme. METHODS: An audit of the documentation of the provisions made for transfer in 10 centres participating in a controlled trial of transitional care. Each centre conducted a retrospective case-note audit of the recent patients transferred to adult care before and 12 - 24 months after commencement of the trial. Demographic details, age when transition was first discussed, age at transfer, transitional issues, multidisciplinary team involvement, adolescent self-advocacy and readiness were documented. RESULTS: There were considerable improvements at follow-up in the documentation of transitional issues, disease-specific educational needs, adolescent readiness and parental needs with the exception of dental care, dietary calcium and home exercise programmes. The age at which the concept of an independent clinic visit was introduced was lower (16.8 +/- 1.06yrs vs 15.8 +/- 1.46yrs, p=0.01) but there were no other changes in the age-related transitional milestones. Significantly more had preparatory visits to the adult clinic, had a transition plan and had joint injections awake at follow up. CONCLUSIONS: The improvement in documentation suggests that involvement in the research project increased awareness of transitional issues beyond the actual study participants. The difficulty of changing policy into practice however is highlighted with room for improvement particularly at the paediatric-adult interface. The reasons for this are likely to be multiple including resources and/or lack of specific training in this area

46. RUPRECHT CR, GATTORNO M, FERLITO F, GREGORIO A, MARTINI A, LANZAVECCHIA A, SALLUSTO F: Coexpression of CD25 and CD27 identifies FoxP3SUP+ regulatory T cells in inflamed synovia. Journal of Experimental Medicine (United States ) 201:11 1793-1803,
    Abstract: A better understanding of the role of CD4SUP+CD25SUP+ regulatory T cells in disease pathogenesis should follow from the discovery of reliable markers capable of discriminating regulatory from activated T cells. We report that the CD4SUP+CD25SUP+population in synovial fluid of juvenile idiopathic arthritis (JIA) patients comprises both regulatory and effector T cells that can be distinguished by expression of CD27. CD4 SUP+CD25SUP+CD27SUP+ cells expressed high amounts of FoxP3 (43% of them being FoxP3SUP+), did not produce interleukin (IL)-2,interferon-gamma, or tumor necrosis factor, and suppressed T cell proliferation in vitro, being, on a per cell basis, fourfold more potent than the corresponding peripheral blood population. Incontrast, CD4 SUP+CD25SUP+CD27S

47. SAULSBURY FT: Lyme arthritis in 20 children residing in a non-endemic area. Clinical Pediatrics (United States ) 44:5 419-421, 2005
    Abstract: In non-endemic areas of the country, Lyme disease may not be considered in children who present with arthritis. This report details the clinical features of Lyme arthritis in 20 children residing in central Virginia. All patients presented with transient, often recurrent oligoarthritis of large joints, particularly the knee. Most patients were referred with a presumptive diagnosis of juvenile rheumatoid arthritis (JRA). This report reiterates the clinical presentation of Lyme arthritis in children and reminds physicians to consider the diagnosis of Lyme arthritis in children who present with acute arthritis even if they reside in a non-endemic area of the country. In addition, it differentiates the clinical presentation of Lyme arthritis from JRA. (c) 2005 Westminster Publications, Inc

48. SAWYER MG, CARBONE JA, WHITHAM JN, ROBERTON DM, TAPLIN JE, VARNI JW, BAGHURST PA: The relationship between health-related quality of life, pain, and coping strategies in juvenile arthritis - A one year prospective study. Quality of Life Research (Netherlands ) 14:6 1585-1598, 2005
    Abstract: The aim of this 12-month prospective study was to compare reports describing the health-related quality of life (HRQL) of children with Juvenile idiopathic arthritis (JIA) obtained from parents and children, to investigate the extent to which the children's HRQL changed over a 12-month period, and to describe the relationship between children's HRQL, and their experience of pain and use of pain coping strategies. Fifty-four children aged 8-18 years with JIA and their parents completed standard questionnaires assessing children's HRQL, pain intensity, and pain coping strategies at baseline, 6 m onths, and 12 months. In general, children reported that their HRQL was better than was reported by parents. Both informants described children's HRQL as being very stable over the 12 months of the study. Consistent with the Biobehavioural Model of Pain, there was a significant negative relationship between children's HRQL and their experience of pain. However, there was little evidence that pain coping strategies mediated the relationship between children's experience of pain and their HRQL. (c) Springer 2005

49. SAXENA N, AGGARWAL A, MISRA R: Elevated concentrations of monocyte derived cytokines in synovial fluid of children with enthesitis related arthritis and polyarticular types of juvenile idiopathic arthritis. J Rheumatol 32:7 1349-1353, 2005
    Organism: Department of Immunology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, IndiaFAU - Saxena, Nandita
    Abstract: OBJECTIVE: Cytokines are the major mediators of joint damage in chronic arthritis. Data on synovial fluid (SF) cytokine concentrations in patients with juvenile idiopathic arthritis (JIA), especially enthesitis related arthritis (ERA), are limited. We measured levels of different monocyte derived cytokines, T cell derived cytokines, and a proinflammatory chemokine in SF specimens from children with ERA or polyarticular (Poly) rheumatoid factor (RF)-negative JIA. METHODS: Macrophage products [tumor necrosis factor-a (TNF-a), interleukin 1ss (IL-1ss), IL-6, IL-12p40)], T lymphocyte products [IL-2, IL-4, interferon-g (IFN-g)], and a proinflammatory chemokine (IL-8) were assayed using ELISA in SF specimens from 53 patients with JIA [ERA 34, polyarticular RF-negative 19] and 40 patients with rheumatoid arthritis (RA). RESULTS: In the ERA group, median SF cytokine levels were higher compared to RA (all values are pg/ml): IL-1ss [< 15.6 (< 15.6-213) vs < 15.6 (< 15.6-41); p < 0.01], IL-12p40 [236 (< 15.6-1714) vs 21 (< 15.6-520); p < 0.0001], and IL-6 [1139 (< 4.6-2187) vs 835 (< 4.6-875); p < 0.0001]. TNF-a and IFN-g levels were similar to RA. IL-8 levels were significantly less than RA (p < 0.0001). The median levels of IL-1ss [39.4 (< 15.6-558) vs < 15.6 (< 15.6-41); p < 0.0001] and IL-12p40 [209 (< 15.6-849) vs 21 (< 15.6-520); p < 0.0001] were higher in patients with Poly-JIA compared to RA. TNF-a, IL-6, and IL-8 levels in Poly-JIA were comparable to RA. IL-2 and IL-4 were not detectable in any patient with JIA. Cytokine profile comparison between the 2 subsets revealed that the median IL-6 [1139 (< 4.6-2187) vs 790 (17.4-2119); p < 0.01] and IFN-g levels [235 (< 4.6-600) vs < 4.6 (< 4.6-412); p < 0.0001] were higher in ERA than in Poly-JIA. In contrast, median IL-8 levels were higher in Poly-JIA [200 (3.8-200)] compared to ERA [74.6 (4-200); p < 0.001]. However, there was no difference in levels of TNF-a, IL-1ss, and IL-12p40 between patients with these 2 subtypes of JIA. CONCLUSION: SF levels of IL-1ss and IL-12p40 are increased in both Poly-JIA and ERA as compared to RA. IL-6 levels were higher in ERA compared to RA. Levels of TNF-a were comparable to RA in both Poly-JIA and ERA. This suggests that joint inflammation in JIA is mediated predominantly by monocytes. In ERA the levels of IL-6 and IFN-g are higher than in Poly-JIA. The increase in IFN-g in children with ERA with undetectable IL-4 suggests a Th1-dominant immune response in this disease subset

50. SAYAH A, ENGLISH JC, III: Rheumatoid arthritis: a review of the cutaneous manifestations. J Am Acad Dermatol 53:2 191-209, 2005
    Organism: Department of Dermatology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USAFAU - Sayah, Anousheh
    Abstract: Rheumatoid arthritis is a chronic inflammatory arthritis with significant extra-articular manifestations. Of note are unique cutaneous manifestations that the dermatologist may encounter. This article will make the dermatologist more cognizant of these skin findings in patients with this systemic inflammatory disorder. It examines rheumatoid arthritis, focusing on the general nonspecific and disease-specific rheumatoid arthritic skin changes. Classic rheumatoid nodules, accelerated rheumatoid nodulosis, rheumatoid nodulosis, rheumatoid vasculitis, Felty syndrome, pyoderma gangrenosum, interstitial granulomatosus dermatitis with arthritis, palisaded neutrophilic and granulomatosis dermatitis, rheumatoid neutrophilic dermatitis, juvenile rheumatoid arthritis, and adult-onset Still disease are reviewed. Understanding the cutaneous expressions of rheumatoid arthritis may lead to early diagnosis, prompt treatment, and lower morbidity and mortality for the affected persons. Learning objective At the completion of this learning activity, participants should be able to describe rheumatoid arthritis in terms of its epidemiology, etiology, pathogenesis, and general and specific cutaneous manifestations

51. SELVAAG AM, LIEN G, SORSKAAR D, VINJE O, FORRE O, FLATO B: Early disease course and predictors of disability in juvenile rheumatoid arthritis and juvenile spondyloarthropathy: A 3 year prospective study. Journal of Rheumatology (Canada ) 32:6 1122-1130, 2005
    Abstract: Objective. To describe the 3 year disease course in early juvenile rheumatoid arthritis (JRA) and juvenile spondyloarthropathy (JSpA), to compare the health status after 3 years of followup with that of normal controls, and to investigate the relationship between physical function at followup and disease characteristics recorded during the first 6 months. Methods: One hundred and ninety-seven children (median age 6.6 yrs) with JRA and JSpA and disease duration < 1.5 years were examined by a pediatric rheumatologist every 6 months for a median of 3.1 years. Controls were randomly selected from the National Population Register. Physical and psychosocial health was assessed by means of the Child Health Questionnaire and the Childhood Health As sessment Questionnaire (CHAQ). Disease course was analyzed by analysis of variance for repeated measurements. Results. Health status and disease activity improved over time. Treatment with disease modifying antirheumatic drugs was started in 58% of the patients at baseline. Patients with persistent oligoarthritis had the most favorable disease course. The patients with juvenile ankylosing spondylitis (JAS), syndrome of seronegative enthesopathy and arthropathy (SEA), and rheumatoid factor (RF) positive polyarthritis had the poorest health status. A significant improvement for the whole group was observed after 3 years in all measures of disease activity and health status, except pain. Patients had poorer physical function and general health and more pain than controls. Predictors of reduced physical function at followup were a high CHAQ disability index and a poor well-being assessed during the first 6 months. Conclusion. Health status and disease activity improved over time in patients under medical treatment. The patients with JAS/SEA and RF positive polyarthritis had poorer health than the patients in other subtypes. A high disability index and a poor well-being at baseline predicted reduced physical function after 3 years

52. SKYTTA ET, BELT EA, KAUTIAINEN HJ, LEHTINEN JT, IKAVALKO M, MAENPAA HM: Use of the de la Caffiniere prosthesis in rheumatoid trapeziometacarpal destruction. Journal of Hand Surgery (United Kingdom ) 30:4 395-400, 2005
    Abstract: This study evaluated the outcome of the de la Caffiniere prosthesis in patients with an inflammatory arthropathy affecting the trapeziometacarpal joint. The procedure was performed in 57 thumbs for rheumatoid arthritis (41 cases), juvenile chronic arthritis (ten cases), psoriatic arthritis (four cases) and other inflammatory joint diseases (two cases). Survival analysis with a revision procedure or radiographic implant failure as end points was performed. Five loosened cups and two permanently dislocated prostheses underwent revision surgery. These were managed with a bone graft and tendon int erposition technique. Radiographic follow-up yielded four additional implant failures (two loosened cups, one loosened metacarpal stem and one permanent dislocation). The implant survival rate based on revision operation was 87% (95% CI 73-94) at 10 years, and the total radiographic and implant failure rate based on radiographic findings was 15% (95% CI 7-29) at 10 years. (c) 2005 The British Society for Surgery of the Hand. Published by Elsevier Ltd. All rights reserved

53. VALTA H, LAHDENNE P, AALTO K, MAKITIE O: Low prevalence of osteoporosis among pediatric patients with juvenile idiopathic arthritis - Protective influence of anti-rheumatic drug combinations? J Bone Miner Res 19: S332, /10/4

54. VOGEL-GERLICHER P, KETTNER H-O, MICHELS H: Etanercept - When and when not? - An overview
    ETANERCEPT - WANN UND WANN NICHT? - EINE UBERSICHT. Aktuelle Rheumatologie (Germany ) 30:3 191-194, 2005
    Abstract: Etanercept was licensed in Europe in 2000 for special forms of juvenile idiopathic arthritis (JIA), and has greatly increased therapeutic options. Nearly 80% of all patients with polyarticular JIA show impressive therapeutic results. Short-to medium term observed adverse drug reactions are manageable. Etanercept is currently licensed only for children of over 4 years of age with poly-articular JIA that failed to respond to methotrexate. Licensed usage is expected to be extended in the near future. Etanercept should only be prescribed by an experienced pediatric rheumatologist. To date there are no recommendations as to when the treatment with etanercept may be stopped once the patient goes into remission. Follow-up is required to exclude long term adverse drug reactions. (c) Georg Thieme Verlag KG Stuttgart

55. VON SCHEVEN E, GORDON CM, GALLAGHER K, WERTZ M, BACHRACH L: Predicting low bone mineral density in childhood inflammatory diseases: Experience from a glaser pediatric research network alendronate trial. J Bone Miner Res 19: S470, /10/4

56. VON SCHEVEN E, GORDON CM, GALLAGHER K, WERTZ M, BACHRACH L: Vitamin D insufficiency is common among pediatric subjects participating in an osteoporosis treatment trial: A glaser pediatric research network study. J Bone Miner Res 19: S470, /10/4

57. WASSERMAN MJ, WEBER DA, GUTHRIE JA, BYKERK VP, LEE P, KEYSTONE EC: Infusion-related reactions to infliximab in patients with rheumatoid arthritis in a clinical practice setting: relationship to dose, antihistamine pretreatment, and infusion number. J Rheumatol 31:10 1912-1917, 2004
    Organism: Rebecca MacDonald Centre for Arthritis and Autoimmune Disease, Division of Advanced Therapeutics, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, CanadaFAU - Wasserman, Michael J
    Abstract: OBJECTIVE: We describe infusion-related reactions to infliximab (during infusion or within 1 hour postinfusion) in patients with active rheumatoid arthritis (RA) treated in a quaternary care center. METHODS: We followed 113 patients for a mean of 60.6 +/- 28.9 weeks, obtaining 10.5 +/- 4.9 infusions per patient. RESULTS: We observed 1183 infusions resulting in 104 infusion reactions (8.8%). All reactions resolved within several hours following cessation of the infusion and none was serious enough to warrant hospitalization. Reactions included allergic reactions (pruritis, urticaria) in 4.2% of infusions, cardiopulmonary (hypotension, hypertension, tachycardia) in 3.0%, and miscellaneous reactions (headache, nausea, vomiting) in 2.0%. Reactions occurred in 8.0% of 3 mg/kg infusions and in 10.3% of 5 mg/kg infusions. Reactions occurred in 13.2% of infusions that involved antihistamine pretreatment compared to only 7.5% of infusions that involved no pretreatment. At both infliximab doses, there was a similar frequency of infusion reactions in patients pretreated due to a previous infusion (12.6%) compared to those pretreated strictly based on infusion number (14.7%). A number of the reactions involving antihistamine pretreatment may be explained by known side effects of diphenhydramine, including headache, dizziness, nausea, and palpitations. CONCLUSION: Infusion-related reactions to infliximab were infrequent, rarely severe, and easily manageable. The frequency of reactions was equivalent in patients treated with 3 mg/kg compared to 5 mg/kg. Reactions were significantly more frequent in infusions where patients were pretreated with the antihistamine diphenhydramine, compared to those not involving pretreatment

58. WELLER F, HUPPERTZ H-I: The pharmacomedical treatment of juvenile idiopathic arthritis
    DIE BEHANDLUNG DES KINDLICHEN RHEUMAS: PHARMAKOTHERAPIE. Zeitschrift fur Rheumatologie (Germany ) 64:5 308-316, 2005
    Abstract: The treatment of juvenile idiopathic arthritis has changed a great deal in the last few years. Pharmacomedical treatment, physiotherapy and teaching the patients and parents are the mainstays of successful therapy. Using all available treatment options and thanks to new therapeutic options (TNFalpha-blockade) and due to a better understanding of the pathogenesis, individual therapeutic strategies provide adequate disease control in the large majority of cases. According to the subtype of juvenile idiopathic arthritis, different medications are used in combination with nonsteroidal antiinflammatory drugs (NSAID) which are used initially. Methotrexate (MTX) and steroids in various applications are the drugs of choice for the systemic and polyarticular courses; intraarticular steroids, sulfasalazine and hydroxychloroquine for the oligoarticular subtype. The new option of TNFalpha-blockade (Etanercept, Infliximab, Adalimumab) offers significant clinical benefit in patients with polyarticular involvement, who do not respond to MTX. Further biological agents (Anakinra, Abatacept, Atlizumab) are used in children and adolescents in clinical studies. Rarely azathioprine, cyclosporine A, leflunomide and cyclophosphamide are used. Stem cell transplantation has been tried as a very last resort but interpretation of the results is controversial. Due to the improvement of the therapeutic options, the approaches to the patients and their disease has changed and cautious optimism is justified. (c) Steinkopff Verlag 2005

59. WILAND P: Role of intravenous immunoglobulin preparations (IVIG) in therapy of autoimmune diseases. Central-European Journal of Immunology (Poland ) 28:1 41-45, 2003
    Abstract: Indications for application of high doses of intravenous immunoglobulin preparations (intravenous immunoglobulins - IVIG) have been significantly broadened in the recent decade. Results of the recent controlled clinical studies have accentuated a particular therapeutic value of IVIG in Kawasaki syndrome. At present, the treatment of choice for acute Kawasaki syndrome is a single dose of IVIG, at 2 gm/kg administered over 10-12 hours, in combination with acetylsalicylic acid. Literature of last years contains reports of variable effectiveness of IVIG in other autoimmune diseases, like anti-phospholipid syndrome, severe forms of thrombocytopenia in the course of systemic lupus erythematosus, some other severe forms of lupus with multiorgan manifestation, dermatomyositis, polymyositis, juvenile dermatomyositis and inclusion body myositis. Attempts were made to administer IVIG in the course of lupus nephritis, systemic vasculitis and in the severe form of systemic juvenile arthritis. On the other hand, no favorable effects of IVIG could be demonstrated in rheumatoid arthritis

60. ZHERNAKOVA A, EERLIGH P, BARRERA P, WESELOY JZ, HUIZINGA TW, ROEP BO, WIJMENGA C, KOELEMAN BP: CTLA4 is differentially associated with autoimmune diseases in the Dutch population. Hum Genet :1-9.: 1-9, 2005
    Organism: Department of Medical Genetics, University Medical Centre, Wilhelmina Children's Hospital, PO Box 85090, 3508, AB, Utrecht, The Netherlands
    Abstract: Cytotoxic T lymphocyte-associated antigen 4 (CTLA4) is an important negative regulator of T-cell response and its genetic association with type 1 diabetes (T1D) has recently been demonstrated. The frequent co-association of autoimmune diseases (AID) and the implication from multiple genome scans that the CTLA4 gene region is a general autoimmune region, led us to study the role of CTLA4 in independent cohorts of T1D, coeliac disease (CD) and rheumatoid arthritis (RA) patients. We present independent data that confirm the association of CTLA4 in Dutch patients with juvenile onset T1D and show differential association of CTLA4 with CD and RA. The CTLA4 gene polymorphisms were tested for association in 350 T1D, 310 CD, 520 RA patients and 900 controls. In addition, 218 families were tested by the transmission disequilibrium test (TDT). T1D patients showed the highest association with the MH30*G: -1147*C: +49*G: CT60*G: JO37_3*G (haplotype 2) in both a case/control cohort (P=0.002, OR=1.42) and by TDT (P=0.02, OR=1.43). In contrast, this haplotype showed no association in the RA and CD cohorts. However, we observed an increased frequency of the MH30*G: -1147*T: +49*A: CT60*G: JO37_3*A (haplotype 3) in the CD patients diagnosed at a young age (OR=1.6, P=0.026, P (c)=0.052). Furthermore, when T1D and CD patients were stratified based on the HLA risk, the T1D susceptible CTLA4 haplotype 2 was over-represented in the high HLA-risk T1D and CD groups. In conclusion, we confirmed association between CTLA4 haplotype 2 and T1D in the Dutch population. Association with another CTLA4 haplotype (haplotype 3) was confirmed for CD, but only in those patients who had an early age of expression. No effect was found between RA and CTLA4. The association of the CTLA4 haplotype 2 with the high-risk HLA genotype in T1D and CD, which share DQ2 as the one of high-risk alleles, might provide a clue to understanding the common genetic background of AID