Bibliography June 2007

  1. ATES A, KINIKLI G, TURGAY M, AKAY Get TOKGOZ G: Effects of rheumatoid factor isotypes on disease activity and severity in patients with rheumatoid arthritis: a comparative study, Clin.Rheumatol., Vol. 26(4), 538-545., 2007
    Organism:Department of Clinical Immunology and Rheumatology, Ankara University, School of Medicine, Ankara, Turkey ates@medicineankaraedutrFAU - Ates, Askin
    Abstract:    The value of rheumatoid factor (RF) isotypes for assessing rheumatoid arthritis (RA) remains debatable. In this study, we have examined the relationships between RF isotypes and disease activity and severity in RA patients. Sixty-two patients with RA, 48 women and 14 men, were studied. RF was measured by nephelometry (RF-N) and IgG-, IgA-, and IgM-RF isotypes were measured using enzyme-linked immunosorbent assay. Serum C-reactive protein and erythrocyte sedimentation rate were also determined. The patients were classified according to disease activity, joint damage, functional status, and presence of pulmonary involvement, rheumatoid nodule, and secondary Sjogren's syndrome. Although the patients with active disease had significantly higher IgA-RF and IgM-RF levels compared to inactive patients, IgA-RF and IgM-RF were not found to be independently associated with disease activity in multivariate analysis. In patients with severe joint damage, IgA-RF and RF-N were significantly higher than those of the other patients. Multiple regression analysis showed that IgA-RF was the unique variable independently associated to severe joint damage. The patients with class III and IV functional index had significantly higher IgM-RF, IgA-RF, and RF-N levels compared to the patients with class I and II functional index; however, RFs were not significantly associated with functional status in multivariate analysis. IgA-RF and IgM-RF were significantly associated with pulmonary involvement and rheumatoid nodule, respectively. No significant associations were found between RF isotypes and secondary Sjogren's syndrome. Our results suggest that the clinical usefulness of IgA and IgM isotypes is better than RF-N. Elevated IgA-RF may be a marker of erosive disease. The usefulness of RF isotypes for monitoring disease activity or functional status appears to be limited

  2. BACHE I, NIELSEN NM, ROSTGAARD K, TOMMERUP Net FRISCH M: Autoimmune diseases in a Danish cohort of 4,866 carriers of constitutional structural chromosomal rearrangements, Arthritis Rheum., Vol. 56(7), 2402-2409., 2007
    Organism:Wilhelm Johannsen Centre for Functional Genome Research, University of Copenhagen, Copenhagen, Denmark
    Abstract:    OBJECTIVE: Constitutional structural chromosomal rearrangements (CSCRs) have facilitated the identification of genes associated with early-onset monogenic disorders and, more recently, genes associated with common and late-onset disorders. In an attempt to find genetic clues to their etiologies, we studied the risk of autoimmune diseases in a Danish cohort of CSCR carriers. METHODS: We followed up 4,866 CSCR carriers over 71,230 person-years (1980 through 2004) for autoimmune diseases recorded in the Danish Hospital Discharge Register. Standardized incidence ratios (SIRs) and 95% confidence intervals (95% CIs) served as measures of the relative risk. To identify possible candidate loci for autoimmune diseases, the reported chromosomal breakpoints and deletions in CSCR carriers who developed autoimmune diseases were compared with previously suggested loci for these diseases. RESULTS: The overall risk of any autoimmune disease among CSCR carriers was inconspicuous (SIR 1.2 [95% CI 0.95-1.5]; n = 74 cases observed versus 61.3 expected), but carriers of rearrangements involving chromosomes 2, 19, and 21 were at significantly increased risk. For the specific autoimmune diseases studied, cohort members were at significantly increased risk of Dupuytren's contracture, pernicious anemia, and juvenile rheumatoid arthritis (JRA). Sixteen carriers who developed an autoimmune disease had a chromosomal breakpoint or deletion coinciding with a previously suggested locus, including deletions 18p11, 18q22, and 22q11 associated with JRA. CONCLUSION: CSCR carriers do not have a generalized predisposition to autoimmune diseases. However, we confirmed a number of reported susceptibility loci for JRA, and we suggest new susceptibility loci on chromosomes 5 and 11 for Dupuytren's contracture, and 19p13 as a possible shared susceptibility locus for a range of autoimmune diseases

  3. BENNANI L, AMINE B, ICHCHOU L, LAZRAK Net HAJJAJ-HASSOUNI N: Progressive pseudorheumatoid dysplasia: Three cases in one family, Joint Bone Spine., Vol. ., 2007
    Organism:Rheumatology Department, El-Ayachi Hospital, Rabat-Sale Teaching Hospital, Rabat-Sale, Morocco
    Abstract:    Progressive pseudorheumatoid dysplasia is an inherited skeletal dysplasia with autosomal recessive transmission. Radiographs of the spine show abnormalities similar to those seen in spondyloepiphyseal dysplasia tarda. The clinical presentation, but not the imaging study findings, suggest juvenile idiopathic arthritis. We report 3 cases of progressive pseudorheumatoid dysplasia in the same family. CASE-REPORTS: A 4-year-old girl had been receiving follow-up for 3 years for seronegative, polyarticular juvenile idiopathic arthritis progressing by flares and remissions. The disease was unresponsive to anti-inflammatory medications. Findings at admission included inflammatory joint pain, joint swelling, range-of-motion limitation, and joint deformities in the hands, wrists, ankles, and knees. The hips were normal. Normal values were found for the erythrocyte sedimentation rate and C-reactive protein level. Synovial fluid removed from one of the knees exhibited mechanical properties. Plain radiographs of the hands and forefeet showed no evidence of joint destruction. Bilateral hip dysplasia was noted on a radiograph of the pelvis. The diagnosis of juvenile idiopathic arthritis was reconsidered. A study of the family identified two similar cases, in a brother and paternal uncle. The brother, who was 14 years old, had similar manifestations without laboratory evidence of inflammation; radiographs disclosed dysplasia of the hips and metacarpophalangeal epiphyses. Manifestations in a paternal uncle consisted of spinal stiffness, thoracic kyphosis, and motion-range limitation at the hips; radiographs showed normal sacroiliac joints and bilateral hip dysplasia. A diagnosis of progressive pseudorheumatoid dysplasia with polyarticular involvement was given. DISCUSSION: Progressive pseudorheumatoid dysplasia is an autosomal recessive disease characterized by abnormal cartilage homeostasis. It should be included among the differential diagnoses of juvenile idiopathic arthritis

  4. BRINKMAN DM, DE KLEER IM, TEN CATE R, VAN ROSSUM MA, BEKKERING WP, FASTH A, VAN TOL MJ, KUIS W, WULFFRAAT NMet VOSSEN JM: Autologous stem cell transplantation in children with severe progressive systemic or polyarticular juvenile idiopathic arthritis: Long-term followup of a prospective clinical trial, Arthritis Rheum., Vol. 56(7), 2410-2421., 2007
    Organism:Leiden University Medical Centre, Leiden, The Netherlands
    Abstract:    OBJECTIVE: To assess the safety and efficacy of intensive immunosuppression followed by T cell-depleted autologous hematopoietic stem cell transplantation (ASCT) for induction of disease remission in children with refractory progressive juvenile idiopathic arthritis (JIA). METHODS: Twenty-two patients with progressive refractory JIA were followed up over a median period of 80 months after pretreatment with intensive immunosuppression followed by ASCT in a multicenter, prospective, phase II clinical trial. Hematopoietic stem cells were harvested from the patients' bone marrow, depleted of T cells, and kept frozen until used for ASCT. Pretreatment of patients consisted of a combination of antithymocyte globulin, cyclophosphamide, and low-dose total body irradiation. Patients were followed up for ASCT-related complications, recovery of hematologic and immune system parameters, and disease outcomes. RESULTS: Reconstitution of hematologic values to normal range was rapid. Recovery of immune system parameters, especially normalization of CD4+, CD45RA+ naive T cells, was delayed, occurring at >/=6 months after ASCT. The prolonged period of immune deficiency resulted in a large number of viral infections and may have contributed to the development of macrophage activation syndrome (MAS), leading to death, in 2 patients. After ASCT, 8 of the 20 evaluable patients reached complete clinical remission of their JIA, 7 were partial responders, and 5 experienced a relapse of their disease (occurring 7 years after ASCT in 1 patient). Later during followup, 2 of the patients whose disease relapsed died from infections that developed after restarting immunosuppressive medication. CONCLUSION: Intensive immunosuppression followed by ASCT resulted in sustained complete remission or marked improvement in 15 of 22 patients with progressive refractory JIA. The procedure, however, is associated with significant morbidity and risk of mortality due to prolonged and severe depression of T cell immunity. After fatal complications due to MAS were observed in some patients, the protocol was amended in 1999, to ensure less profound depletion of T cells, better control of systemic disease before transplantation, antiviral prophylaxis after transplantation, and slow tapering of corticosteroids. Following these protocol modifications, no additional ASCT-related deaths were observed among the 11 patients who received the modified treatment

  5. COBO-IBANEZ Tet MARTIN-MOLA E: Etanercept: long-term clinical experience in rheumatoid arthritis and other arthritis, Expert.Opin.Pharmacother., Vol. 8(9), 1373-1397., 2007
    Organism:Hospital Universitario La Paz, Servicio de Reumatologia, Paseo de la Castellana 261, 28046 Madrid, SpainFAU - Cobo-Ibanez, T
    Abstract:    Etanercept is a dimeric fusion protein based on the p75 TNF-alpha receptor. It binds to TNF-alpha and blocks its biologic activity. In randomized, double-blind, placebo-controlled trials, etanercept has therapeutic activity in rheumatoid arthritis, psoriatic arthritis, polyarticular-course juvenile idiopathic arthritis and ankylosing spondylitis. Etanercept improves joint inflammation, physical function and slows/halts structural damage, especially when combined with methotrexate. A sustained response is observed in a substantial percentage of patients. Although some safety issues should be considered before starting etanercept treatment, in general terms, etanercept is a well tolerated drug with an acceptable safety profile. The use of any TNF-alpha antagonist must be in agreement with the National Recommendations for Biologic Therapy, and in difficult clinical situations, a balance between risk/benefit needs to be obtained

  6. DUCOS dL, TERRADA C, KODJIKIAN L, TRAN CT, CASSOUX N, LEHOANG Pet BODAGHI B: Maculopathy in uveitis of Juvenile Idiopathic Arthritis- An Optical Coherence Tomography study, Br.J.Ophthalmol., Vol. ., 2007
    Organism:La Pitie Salpetriere Hospital, France
    Abstract:    AIM: To examine the frequency and characteristics of macular lesions observed in Juvenile Idiopathic Arthritis (JIA) uveitis, using Optical Coherence Tomography (OCT). METHODS: In this cross-sectional study, 38 consecutive patients were recruited from a tertiary referral center in uveitis. All eyes with JIA uveitis underwent complete ophthalmic examination including OCT 3. Exclusion criterion was the inability to obtain OCT scans. Flare and visual acuity were also analysed by using linear regression. RESULTS: We analyzed foveal thickness (FT) and central foveal thickness (CFT) using the software mapping, to describe macular lesions in 61 eyes. Maculopathy was observed in 51 eyes (84%), compared to 12% in the literature (P<0.0001) and comprised four types: perifoveolar thickening in 45 eyes (74%), macular edema in 29 eyes (48%), foveal detachment in 11 eyes (18%), and atrophic changes in 6 eyes (10%). Only 4 eyes did not demonstrate any lesion. CONCLUSIONS: Among children with JIA-uveitis, macular involvement is frequent, and characterized by perifoveolar thickening and serous retinal detachment. OCT is a non-invasive instrument. It may easily shows this maculopathy, which could impair visual function

  7. ENGSTROM AL, WANMAN A, JOHANSSON A, KESHISHIAN Pet FORSBERG M: Juvenile arthritis and development of symptoms of temporomandibular disorders: a 15-year prospective cohort study, J.Orofac.Pain., Vol. 21(2), 120-126., 2007
    Organism:Department of Clinical Oral Physiology, Faculty of Medicine, Gothenburg University, Gothenburg, Sweden Anna-LenaEngstrom@odontologiguseFAU - Engstrom, Anna-Lena
    Abstract:    AIMS: To compare the development of symptoms of temporomandibular disorders (TMD) in a sample of patients with juvenile arthritis (JA) and a matched control sample. METHODS: In 1986, 40 patients with JA (28 girls and 12 boys; mean age +/- SD, 18 +/- 4.5 years) and an age- and sex-matched control sample were examined for signs and symptoms of TMD. Fifteen years later in 2001, a questionnaire concerning symptoms of TMD was sent to these subjects. Twenty-eight individuals (68%) in the JA sample (20 women and 8 men; mean age +/- SD, 35 +/- 5.2 years) and 26 controls (19 women and 7 men; 34 +/- 4.0 years) were available for the follow-up. RESULTS: The overall prevalence of symptoms of TMD increased between the 2 examinations in both groups. The prevalence of reported TMD symptoms, such as jaw pain, fatigue in the jaws, and difficulty opening the jaws wide, as well as awareness of tooth clenching, headaches, neck and shoulder pains, was significantly greater among the JA sample than among the controls at the follow-up. CONCLUSION: The study indicates that prevalence of pain and dysfunction in the craniofacial or cervical regions of JA patients is increased more than 20 years after the onset of JA compared to healthy individuals

  8. FLICINSKI J, MILCHERT M, OSTANEK L, BRZOSKO I, PRZEPIERA-BEDZAK H, PRAJS Ket BRZOSKO M: [Adult-onset Still's disease], Ann.Acad.Med.Stetin., Vol. 52 Suppl 2, 111-114., 2006
    Organism:Klinika Reumatologii Pomorskiej Akademii Medyczne, ul Unii Lubelskiej 1, 71-252 SzczecinFAU - Flicinski, Jacek
    Abstract:    INTRODUCTION: The authors present the course and manifestations of adult-onset Still's disease on the basis of five cases diagnosed at the Department of Rheumatology, Pomeranian Medical University in Szczecin. MATERIAL AND METHODS: The usefulness of two most popular sets of diagnostic criteria of adult-onset Still's disease (Yamaguchi and Cush) was analyzed. At onset of the disease, two out of five patients met both sets of the diagnostic criteria, two others met criteria of Yamaguchi and one of Cush. During follow-up, criteria of Yamaguchi were met in all cases. RESULTS: The authors suggest to use the Cushs criteria of adult-onset Still's disease when the patient does not meet the criteria of Yamaguchi and other causes of fever are excluded

  9. GALLAGHER MJ, QUINONES K, CERVANTES-CASTANEDA RA, YILMAZ Tet FOSTER CS: Biologic Response Modifier Therapy for Refractory Childhood Uveitis, Br.J.Ophthalmol., Vol. ., 2007
    Organism:MERSI, United States
    Abstract:    PURPOSE: To evaluate the use of biologic response modifiers (BRM's) in the treatment of refractory childhood uveitis. DESIGN: Retrospective non comparative case series of pediatric patients with uveitis treated with BRM's. PARTICIPANTS: 23 pediatric patients. METHODS: All children (18 years or younger) who received a BRM were assessed for visual changes, time to control inflammation, and any associated adverse side effects. Thirteen patients were treated with infliximab, five with adalimumab, and five with daclizumab. All patients had bilateral eye involvement. Diagnoses of the participants included juvenile idiopathic arthritis, keratouveitis, sarcoid panuveitis, Adamantiades- Behcets disease, and idiopathic panuveitis. MAIN OUTCOME MEASURES: Inflammation and visual acuity. RESULTS: In the infliximab group 16 of 26 (62%) eyes, and 10 of 13 (77%) patients demonstrated an improvement in visual acuity. Twenty of 26 (77%) patients demonstrated an improvement in the degree of inflammation. In the adalimumab group 4 of 10 (40%) eyes demonstrated an improvement in visual acuity with 5 of 10 (50%) patients demonstrating an improvement in inflammation. Four of 10 (40%) eyes in the daclizumab group demonstrated an improvement in vision with 8 of 10 (80%) patients demonstrating an improvement in inflammation. CONCLUSIONS: BRM's appear to be safe to use in children, and represent a useful therapeutic adjunctive drug group for treating recalcitrant childhood uveitides

  10. GARCIA-CARRASCO M, FUENTES-ALEXANDRO S, ESCARCEGA ROet ROJAS-RODRIGUEZ J: [Systemic juvenile rheumatoid arthritis], Rev.Med.Inst.Mex.Seguro.Soc., Vol. 45(2), 187-188., 2007
    Organism:

  11. GARTLEHNER G, HANSEN RA, JONAS BL, THIEDA Pet LOHR KN: Biologics for the treatment of juvenile idiopathic arthritis: a systematic review and critical analysis of the evidence, Clin.Rheumatol., Vol. ., 2007
    Organism:Ludwig Boltzmann Institute for Health Technology Assessments, Garnisongasse 7/20, 1090, Vienna, Austria, gartlehner@schsruncedu
    Abstract:    Biologics are an important therapeutic option for treating patients with juvenile idiopathic arthritis (JIA). In adults, they are associated with rare but severe adverse events such as serious infections and malignancies. We reviewed systematically the evidence on the efficacy and safety of biologics for the treatment of JIA. We searched electronic databases up to August 2006. We limited evidence to prospective studies for efficacy but included retrospective observational evidence for safety. Outcomes of interest were clinical response, radiographic progression, quality of life, and adverse events. One randomized controlled trial (RCT) and 11 uncontrolled prospective studies provided data on efficacy; three additional studies assessed safety. The only RCT and six uncontrolled trials support the general efficacy of etanercept for the treatment of JIA. Internal and external validity of these studies are limited. The evidence on other biologic agents such as adalimumab, abatacept, anakinra, infliximab, rituximab, and tocilizumab is sparse or entirely missing. Because of the lack of sound long-term safety data, evidence is insufficient to draw firm conclusions about the balance of risks and benefits of any biologic agent for the treatment of JIA. Clinicians have to be aware of the lack of evidence supporting a long-term net benefit when considering biologics for patients with JIA

  12. GATTORNO M, CHICHA L, GREGORIO A, FERLITO F, ROSSI F, JARROSSAY D, LANZAVECCHIA A, MARTINI Aet MANZ MG: Distinct expression pattern of IFN-alpha and TNF-alpha in juvenile idiopathic arthritis synovial tissue, Rheumatology (Oxford)., Vol. 46(4), 657-665., 2007
    Organism:Second Division of Pediatrics, G Gaslini Institute and University of Genoa, Largo G Gaslini 5, 16147, Genoa, Italy marcogattorno@ospedale-gaslinigeitFAU - Gattorno, M
    Abstract:    OBJECTIVES: Recent laboratory and clinical data suggest that two prototype autoimmune diseases, systemic lupus erythematosus and rheumatoid arthritis are mainly driven by distinct cytokines, interferon (IFN)-alpha and tumour necrosis factor (TNF)-alpha, respectively. We here investigated the presence and characteristics of natural type I IFN-producing cells (IPCs), as well as IFN-alpha and TNF-alpha expression at sites of inflammation in juvenile idiopathic arthritis (JIA). METHODS: Peripheral blood (PB) and synovial fluid (SF) mononuclear cells (MNCs) (n = 25 each) from JIA patients with active disease were studied. IPCs were identified as BCDA-2(+)CD123(+)HLA-DR(+)CD45RA(+) cells, and dendritic cells (DCs) as CD11c(+)CD14(-/low)lin(-) cells by flow cytometry. IPCs and DCs were analysed for Toll-like receptor-7 and -9 mRNA expression by real-time polymerase chain reaction. IFN-alpha was measured by enzyme-linked immunosorbent assay in serum, SF and in supernatants of influenza virus-infected, cultured IPCs. Synovial tissues of n = 6 additional JIA patients were analysed by immunohistochemistry using mAbs against CD123, IFN-alpha, TNF-alpha, CD3, CD19 and CD138. RESULTS: IPCs were enriched in SF MNCs compared with PB MNCs in all JIA patients. Influenza-induced, but no spontaneous IFN-alpha release was detected from SF IPCs, and serum and SF IFN-alpha levels were not elevated. Nonetheless, in synovial tissue IFN-alpha producing cells accumulated at inflammatory lymph-follicular-like structures, while TNF-alpha producing cells were mostly found at the lining and sublining layers. CONCLUSIONS: These data suggest that besides TNF-alpha-expressing cells, IFN-alpha-producing IPCs are involved in initiation, maintenance or regulation of the inflammatory response in JIA

  13. GONCALVES M, D'ALMEIDA V, GUERRA-SHINOHARA EM, GALDIERI LC, LEN CAet HILARIO MO: Homocysteine and lipid profile in children with Juvenile Idiopathic Arthritis, Pediatr.Rheumatol.Online.J., Vol. 5, 2, 2007
    Organism:Department of Pediatrics, Universidade Federal de Sao Paulo (Unifesp), Sao Paulo, Brazil odetehilario@terracombrFAU - Goncalves, Marcela
    Abstract:    ABSTRACT: BACKGROUND: An increased concentration of plasma homocysteine (Hcy) has toxic effects on vascular endothelium. This seems to be a risk factor of cardiovascular disease, premature stroke and venous thrombosis. The risk is higher in coincidence with other factors like chronic diseases and familiar hypercholesterolemia. The aim of our study was to evaluate plasma Hcy concentration in patients with juvenile idiopathic arthritis (JIA) and its correlation with methotrexate (MTX) therapy, serum folate and B12 vitamin, and hyperlipidemia. METHODS: Fifty-one patients (37 females; mean age 11.3 years, range 2.3-17 years) with JIA and 52 healthy controls (42 females; mean age 12.5 years; range 3-18 years) were included in the study. Thirty-two patients were using weekly MTX (mean doses: 0.1-1 mg/kg). For statistical analysis both JIA and control groups were distributed in three subgroups according to age (3 - 7, 8 - 12 and 13 - 18 years). The laboratory investigation included measurement of erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), plasma Hcy, serum folate, vitamin B12, triglycerides, total cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL) and very low-density lipoprotein (VLDL). For data analysis, we considered raised Hcy values >/= 12.56 mumol/L, which corresponds to the 90th percentile observed in the control group. RESULTS: The mean plasma Hcy concentration was 9.3 +/- 3.16 mumol/L in JIA patients and 8.9 +/- 2.42 mumol/L in healthy controls (p = 0.615). Higher concentration of Hcy was observed in the subgroup of 13 - 18 years (patients and controls, p < 0.001). We did not find correlation between MTX use and plasma Hcy concentration. With regard to vitamin B12 concentration, we detected normal values in both patients and controls while serum folate concentration was higher in patients (p < 0.001). With regard to the lipidogram, lower concentration of HDL was found in patients (p = 0.007) and higher levels of VLDL (p = 0.014) and triglycerides (p = 0.001) were observed in controls. We did not observe correlation among plasma Hcy concentration, clinical findings, ESR and CRP. CONCLUSION: JIA patients do not present significant increased concentration of Hcy despite the use of MTX, probably due to the folate supplementation. The mild abnormalities in the lipidogram may reflect a current concern with diet and health

  14. GURAIEB-IBARROLA Ret GURAIEB-CHAHIN P: [Comments about the article "systemic juvenile rheumatoid arthritis"], Rev.Med.Inst.Mex.Seguro.Soc., Vol. 45(2), 189, 2007
    Organism:

  15. HEILIGENHAUS A, SZURMAN Pet HEINZ C: [Current cataract surgery for uveitis in childhood.], Ophthalmologe., Vol. %19;., 2007
    Organism:Uveitis-Zentrum, Augenabteilung am St Franziskus Hospital, Hohenzollernring 74, 48145, Munster, Deutschland, arndheiligenhaus@uveitis-zentrumde
    Abstract:    Cataract formation is a frequent complication in childhood uveitis. The management of cataracts in childhood uveitis may be particularly difficult. Patient selection is important for successful surgery. Preoperative evaluation is required in order to specify the course and etiology of uveitis. Complete quiescence of the inflammation in required before surgery. The surgical trauma should be minimized. Intraocular lens implantation may be proposed for selected uveitis children and may be considered in well controlled juvenile idiopathic arthritis associated uveitis, e.g. with the use of immunosuppressive drugs or TNF-alpha inhibitors. Postoperatively, the anti-inflammatory medication must be increased and continued for 8-10 weeks

  16. HEILIGENHAUS A, HORNEFF G, GREINER K, MACKENSEN F, ZIERHUT M, FOELDVARI Iet MICHELS H: [Inhibitors of Tumour Necrosis Factor-alpha for the Treatment of Arthritis and Uveitis in Childhood.], Klin.Monatsbl.Augenheilkd., Vol. 224(6), 526-531., 2007
    Organism:Augenabteilung am St Franziskus Hospital, Munster; Universitat Duisburg-EssenFAU - Heiligenhaus, A
    Abstract:    BACKGROUND: Chronic uveitis in childhood is a common complication of juvenile idiopathic arthritis (JIA) that frequently leads to loss of vision. Besides from corticosteroids and immunosuppressive drugs, Tumour necrosis factor-alpha (TNF-alpha) inhibitors are used frequently. MATERIALS AND METHODS: The literature published before September 2006 was evaluated for the usefulness of TNF-alpha inhibitors (etanercept, infliximab, adalimumab) for the treatment of JIA-associated uveitis. RESULTS: TNF-alpha inhibitors are effective drugs for the treatment of chronic uveitis in childhood. The response rate of uveitis in childhood to etanercept was approximately 50 %. However, disease recurrence, first manifestations of uveitis and new complications occurred during the treatment. Infliximab and adalimumab appear to be more effective for the treatment of uveitis in childhood than etanercept. CONCLUSIONS: The therapy with TNF-alpha inhibitors is expensive and increases the long-term risk for secondary diseases, such as tuberculosis and probably malignant lymphoma. Their use should be restricted to uveitis patients not responding to corticosteroids and at least one of established immunosuppressive drugs

  17. HENDRICKX G, DEMANET Cet VANDENPLAS Y: Persistent synovitis in two children with Lyme arthritis linked with HLA-DRB1*1104, Eur.J.Pediatr., Vol. 165(6), 420-421., 2006
    Organism:Department of Paediatrics, Paediatric Orthopaedic and Rheumatology Unit, Academisch Ziekenhuis -Vrije Universiteit Brussel, Laarbeeklaan 101, 1090 Brussels, Belgium ghendrickx@st-annanlFAU - Hendrickx, Guy
    Abstract:

  18. HO PY, BARTON A, WORTHINGTON J, THOMSON W, SILMAN AJet BRUCE IN: HLA-Cw6 and HLA-DRB1*07 together are associated with less severe joint disease in psoriatic arthritis, Ann.Rheum.Dis., Vol. 66(6), 807-811., 2007
    Organism:ARC-EU, Stopford Building, University of Manchester, Oxford Road, Manchester M13 9PT, UK paulineho@manchesteracukFAU - Ho, Pauline Y P C
    Abstract:    BACKGROUND: Human leucocyte antigen (HLA) genes predict disease severity in psoriasis (HLA-Cw6) and rheumatoid arthritis (shared epitope (SE)), but the situation is unclear for psoriatic arthritis (PsA). AIM: To determine the association of the HLA-Cw6 and HLA-DRB1 gene with disease severity in a large UK cohort with PsA. METHODS: Genotyping of the HLA-Cw and HLA-DRB1 loci was undertaken in DNA samples from patients with PsA (n = 480). Stratification and regression analysis were used within the PsA cases to determine whether HLA-Cw6, HLA-DRB1 or the presence of the SE alleles predicted disease severity as measured by the Health Assessment Questionnaire score, the total number of damaged or involved joints adjusted for disease duration and disease-modifying antirheumatic treatments. RESULTS: HLA-Cw6 was found to be in linkage disequilibrium with HLA-DRB1*07 (r(2) = 0.46). Patients with PsA who carried both HLA-Cw6 and HLA-DRB1*07 had fewer damaged or involved joints (41% fewer damaged (95% CI 23% to 55%, p = 0.02) and 31% fewer involved joints (95% CI 16% to 44%, p<0.001)) compared with those who carried neither HLA-Cw6 nor HLA-DRB1*07 alleles. Those who carried either HLA-Cw6 or HLA-DRB1*07 alleles alone had no evidence of a reduction in joint involvement. The SE, HLA-DRB1*03 and HLA-DRB1*04 alleles did not predict severity using these outcome measures. CONCLUSION: Patients with PsA carrying both HLA-Cw6 and HLA-DRB1*07 alleles have a less severe course of arthritis. This suggests that a protective locus lies on a haplotype marked by these alleles. No association was detected with disease severity and SE status

  19. JARVIS JN, JIANG K, PETTY HRet CENTOLA M: Neutrophils: The forgotten cell in JIA disease pathogenesis, Pediatr.Rheumatol.Online.J., Vol. 5(1), 13, 2007
    Organism:ABSTRACT: Juvenile idiopathic arthritis (JIA) has long been assumed to be an autoimmune disease, triggered by aberrant recognition of self antigens by T-cells. However, systems biology approaches to this family of diseases have suggested complex interactions between innate and adaptive immunity that underlie JIA. In particular, new data suggest an important role for neutrophils in JIA pathogenesis. In this short review, we will discuss the new data that support a role for neutrophils in JIA, discuss regulatory functions that link neutrophils to adaptive immune responses, and discuss future areas of investigation. Above all else, we invite the reader to re-consider the use of the term autoimmunity as applied to the family of illnesses we collectively call JIA

  20. JELUSIC M, LUKIC IK, TAMBIC-BUKOVAC L, DUBRAVCIC K, MALCIC I, RUDAN Iet BATINIC D: Interleukin-18 as a mediator of systemic juvenile idiopathic arthritis, Clin.Rheumatol., Vol. 26(8), 1332-1334., 2007
    Organism:Division of Paediatric Rheumatology, Department of Paediatrics, Zagreb University Hospital Centre, Salata 4, Zagreb, HR-10000, Croatia, marijajelusic@inethrFAU - Jelusic, Marija
    Abstract:    The objective of this report is to explore the balance between serum and synovial fluid levels of interleukin (IL)-18 in children with juvenile idiopathic arthritis (JIA). Blood samples were obtained from 81 children with JIA and 18 control children. Synovial fluid samples were collected from 16 children with oligoarticular JIA. Concentrations of IL-18 were determined using commercial kit. Patients with systemic JIA had higher serum levels of IL-18 than patients with other forms of JIA or control children, both during the active (median, range: 6,240, 1,600-78,750 pg/ml) and inactive (1,615, 513-3,270 pg/ml) phase of disease [analysis of variance (ANOVA), P < 0.05). Levels of IL-18 in sera of children with oligoarticular JIA (255, 89-4,342 pg/ml) were similar to the respective synovial fluid levels (217, 89-1,245 pg/ml). Serum levels of IL-18 were proportional to the erythrocyte sedimentation rate and levels of C-reactive protein, but inversely proportional to the haemoglobin levels. IL-18 appears to be an important mediator of systemic JIA, while it seems of a lesser relevance in pathogenesis of other JIA forms. Therefore, inhibition of IL-18 might be a base for a successful biological therapy for systemic JIA

  21. LACHMANN HJ, GOODMAN HJ, GILBERTSON JA, GALLIMORE JR, SABIN CA, GILLMORE JDet HAWKINS PN: Natural history and outcome in systemic AA amyloidosis, N.Engl.J.Med., Vol. 356(23), 2361-2371., 2007
    Organism:National Amyloidosis Centre and Centre for Amyloidosis and Acute Phase Proteins, Department of Medicine, Royal Free and University College Medical School, LondonFAU - Lachmann, Helen J
    Abstract:    BACKGROUND: Deposition of amyloid fibrils derived from circulating acute-phase reactant serum amyloid A protein (SAA) causes systemic AA amyloidosis, a serious complication of many chronic inflammatory disorders. Little is known about the natural history of AA amyloidosis or its response to treatment. METHODS: We evaluated clinical features, organ function, and survival among 374 patients with AA amyloidosis who were followed for a median of 86 months. The SAA concentration was measured serially, and the amyloid burden was estimated with the use of whole-body serum amyloid P component scintigraphy. Therapy for inflammatory diseases was administered to suppress the production of SAA. RESULTS: Median survival after diagnosis was 133 months; renal dysfunction was the predominant disease manifestation. Mortality, amyloid burden, and renal prognosis all significantly correlated with the SAA concentration during follow-up. The risk of death was 17.7 times as high among patients with SAA concentrations in the highest eighth, or octile, (>or=155 mg per liter) as among those with concentrations in the lowest octile (<4 mg per liter); and the risk of death was four times as high in the next-to-lowest octile (4 to 9 mg per liter). The median SAA concentration during follow-up was 6 mg per liter in patients in whom renal function improved and 28 mg per liter in those in whom it deteriorated (P<0.001). Amyloid deposits regressed in 60% of patients who had a median SAA concentration of less than 10 mg per liter, and survival among these patients was superior to survival among those in whom amyloid deposits did not regress (P=0.04). CONCLUSIONS: The effects of renal dysfunction dominate the course of AA amyloidosis, which is associated with a relatively favorable outcome in patients with SAA concentrations that remain in the low-normal range (<4 mg per liter)

  22. LEQUERRE T, VITTECOQ O, SAUGIER-VEBER P, GOLDENBERG A, PATOZ P, FREBOURG Tet LE L, X: A cryopyrin-associated periodic syndrome with joint destruction, Rheumatology (Oxford)., Vol. 46(4), 709-714., 2007
    Organism:Department of Rheumatology, Rouen University Hospital, 76031 Rouen, Cedex, France thierrylequerre@univ-rouenfrFAU - Lequerre, T
    Abstract:    OBJECTIVE: Describe four generations (11 members) of a family with a cryopyrin-associated periodic syndrome (CAPS), including joint destruction, associated with a CIAS1-gene mutation and good responses to anakinra. METHODS: In addition to detailed questioning and physical examination, six family members underwent haematological, immunological and biochemical testing. Exon 3 of the CIAS1 gene was sequenced in search of a mutation in the 1q44 region. RESULTS: During childhood or adolescence, four family members developed different combinations of the following CAPS manifestations: deafness (3/4); arthritis (4/4) with joint destruction for two of them; nervous (cerebral demyelinization, 2/4), cutaneous (livedo and/or urticaria, 3/4) and eye lesions (episcleritis and/or papilloedema, 4/4); IgA hypergammaglobulinaemia (4/4) and inflammatory syndrome (3/4). Sequencing of six family members' CIAS1-gene exon 3 identified a heterozygous mutation, c.1043C > T. Pertinently, this CAPS is distinct from chronic infantile neurological cutaneous and arthritis syndrome/neonatal onset multisystemic inflammatory disease syndrome and Muckle-Wells syndrome (MWS), which also result from exon 3 mutations in this gene. Moreover, this family did not have the usual neurological manifestations, typical morphological features and frequent amyloidosis of MWS. CONCLUSIONS: We describe a previously unreported form of CAPS with atypical neurological signs, joint destruction and livedo. This observation extends the clinical spectrum associated with CIAS1 mutations. Anakinra, an interleukin-1-receptor antagonist, prescribed to two family members, was highly effective

  23. LINDNER E, NORDANG GB, MELUM E, FLATO B, SELVAAG AM, THORSBY E, KVIEN TK, FORRE OTet LIE BA: Lack of association between the chemokine receptor 5 polymorphism CCR5delta32 in rheumatoid arthritis and juvenile idiopathic arthritis, BMC.Med.Genet., Vol. 8(1), 33, 2007
    Organism:ABSTRACT: BACKGROUND: The chemokine receptor CCR5 has been detected at elevated levels on synovial T cells, and a 32 bp deletion in the CCR5 gene leads to a non-functional receptor. A negative association between the CCR5delta32 and rheumatoid arthritis (RA) has been reported, although with conflicting results. In juvenile idiopathic arthritis (JIA), an association with CCR5 was recently reported. The purpose of this study was to investigate if the CCR5delta32 polymorphism is associated with RA or JIA in Norwegian cohorts. METHODS: 853 RA patients, 524 juvenile idiopathic arthritis (JIA) patients and 658 controls were genotyped for the CCR5delta32 polymorphism. RESULTS: The CCR5delta32 allele frequency was 11.5% in the controls vs. 10.4% in RA patients (OR=0.90; P=0.36) and 9.7% in JIA patients (OR=0.85; P=0.20). No decreased homozygosity was observed for CCR5delta32, as previously suggested. CONCLUSIONS: Our data do not support an association between the CCR5delta32 polymorphism and Norweigian RA or JIA patients. Combining our results with those from a recently published meta-analysis still provide evidence for a role for CCR5delta5 in RA, albeit substanially weaker than the effect first reported

  24. MACRAE VE, WONG SC, SMITH W, GRACIE A, MCINNES I, GALEA P, GARDNER-MEDWIN J, FARQUHARSON Cet AHMED SF: Cytokine profiling and in vitro studies of murine bone growth using biological fluids from children with juvenile idiopathic arthritis, Clin.Endocrinol.(Oxf)., Vol. ., 2007
    Organism:Department of Child Health, Royal Hospital for Sick Children, Glasgow, UK
    Abstract:    Objective Growth retardation in children with chronic inflammatory disease may be partly due to direct effects of pro-inflammatory cytokines on the growth plate and requires further investigation. Design This study assessed the cytokine concentrations in serum and synovial fluid (SF) in juvenile idiopathic arthritis (JIA), and determined the effect of the biological fluid on cultured murine metatarsal growth. Patients Serum and SF were obtained from four children attending for arthrocentesis (child A, systemic; children B, C and D, oligoarticular). In addition, serum samples were obtained from four more children (children E and F, polyarticular; child G, oligoarticular). Measurements Anthropometry, cytokine levels and longitudinal bone growth were assessed. Results Cytokines were elevated to a variable extent in the samples. Although all serum samples were associated with reduced metatarsal growth, only SF from child A and child B reduced metatarsal growth. Metatarsals treated with child A's SF showed reduced proliferation, reduced proliferative and mineralizing zone width, and increased hypertrophic zone width. Tumour necrosis factor (TNF)-alpha, interleukin (IL)-1beta and IL-6 concentrations were elevated in child A's SF. However, SF exposure with neutralizing antibodies to these cytokines or IGF-1 did not improve metatarsal growth. Conclusion SF and serum JIA samples can impair bone growth at the growth plate. In synovial fluid, the effect is variable but resistant to treatment with IL-1beta, IL-6 and TNF-alpha specific antibodies and IGF-1, suggesting that other factors in this biological fluid may also have an effect on longitudinal growth through IGF-1-independent mechanisms

  25. MARTI P, MOLINARI L, BOLT IB, SEGER Ret SAURENMANN RK: Factors Influencing the efficacy of intra-articular steroid injections in patients with juvenile idiopathic arthritis, Eur.J.Pediatr., Vol. ., 2007
    Organism:Department of Paediatrics, University Children's Hospital, Zurich, Switzerland
    Abstract:    A retrospective chart review was performed of all patients with juvenile idiopathic arthritis (JIA) followed at our clinic who had an intra-articular steroid injection between 1 January 1997 and 31 December 2001. The aim of the study was to evaluate the outcome of intra-articular steroid injections (iaS) and determine prognostic factors. During the study period, 202 iaS were performed in 60 patients, of whom 37 had oligoarticular JIA, 15 had polyarticular, rheumatoid factor-negative JIA and four each had systemic and enthesitis-related JIA. The median duration of remission was 23.1 months (range: 0-69 months). At last follow-up, 103 joints (51%) of 47 patients were still in remission after a median follow-up time of 28 months (range: 1-69 months). For the total cohort, the remission was longer for wrist and finger joints [risk ratio (RR): 0.2], with concomitant treatment with methotrexate (RR: 0.28) and for enthesitis-related arthritis (RR: 0.34). For the group of knee joints, remission was longer with concomitant treatment with methotrexate (RR: 0.37), with triamcinolone hexacetonide (RR: 0.77) and with general anaesthesia for the procedure (RR: 0.56). Mild side effects were observed in 45 iaS (22.3%), and skin atrophy occurred at the injection site in 2% of injections, but no major adverse event occurred in our cohort. In conclusion, iaS is a safe procedure with a median duration of remission of 23.1 months. The remission was longer in the joints of the upper extremity, with concomitant treatment with methotrexate and when the injection was performed under general anaesthesia

  26. MASSA M, PASSALIA M, MANZONI SM, CAMPANELLI R, CIARDELLI L, YUNG GP, KAMPHUIS S, PISTORIO A, MELI V, SETTE A, PRAKKEN B, MARTINI Aet ALBANI S: Differential recognition of heat-shock protein dnaJ-derived epitopes by effector and Treg cells leads to modulation of inflammation in juvenile idiopathic arthritis, Arthritis Rheum., Vol. 56(5), 1648-1657., 2007
    Organism:Fondazione IRCCS Policlinico San Matteo, Pavia, ItalyFAU - Massa, Margherita
    Abstract:    OBJECTIVE: To identify epitopes on Escherichia coli heat-shock protein (HSP) dnaJ or on homologous human HSP dnaJ involved in the induction/modulation of autoimmune inflammation in patients with oligoarticular juvenile idiopathic arthritis (JIA). METHODS: We used a proliferation assay and cytokine production to evaluate the immune responses of synovial fluid mononuclear cells (SFMCs) to pan-HLA-DR binder peptides derived from either homologous or nonhomologous regions on bacterial and human HSP dnaJ. Cytofluorometric analysis was performed in order to phenotype and sort Treg cells. Sorted cells were then analyzed for the expression of the forkhead box P3 (FoxP3) transcription factor, and their regulatory capacity was tested in coculture assays. RESULTS: T cell responses to E coli HSP dnaJ-derived peptides were eminently proinflammatory. Conversely, peptides derived from human HSP dnaJ induced interleukin-10 (IL-10) production from SFMCs of patients with oligoarticular JIA. A positive correlation was found between disease with a better prognosis (persistent oligoarticular JIA) and recognition of 3 human HSP dnaJ-derived peptides. The recognition of the human peptide H134-148 also induced a significantly greater amount of IL-10 in patients with persistent oligoarticular JIA than in those with extended oligoarticular JIA (P = 0.0012). Incubation of SFMCs from patients with persistent oligoarticular JIA with this human epitope increased the percentage of Treg cells and FoxP3 expression. It also induced the recovery of suppressor activity by Treg cells. CONCLUSION: This is the first description of a self-regulating immune modulator circuit active during autoimmune inflammation through recognition of HSP epitopes with different functional properties. These epitopes induce T cells with regulatory function. Such induction correlates with disease severity and prognosis

  27. MICHELS H, GREINER K, HEINZ C, HORNEFF Get GANSER G: [Other Rheumatic Diseases with Uveitis besides Juvenile Idiopathic Arthritis.], Klin.Monatsbl.Augenheilkd., Vol. 224(6), 473-476., 2007
    Organism:Deutsches Zentrum fur Kinder- und Jugendrheumatologie, Garmisch-Partenkirchen (Leitung: Dr H Michels)FAU - Michels, H
    Abstract:    In childhood and adolescence, uveitis is part of the clinical spectrum of many inflammatory-rheumatic diseases. Besides juvenile idiopathic arthritis juvenile, ankylosing spondylitis, infection-associated arthritides, infantile sarcoidosis, systemic vasculitides, inflammatory bowel diseases, hereditary autoinflammatory syndromes and the TINU syndrome have to be excluded. These inflammatory diseases can be differentiated clinically in connection with immunogenetic and molecular genetic investigations. Early diagnosis of uveitis as well as the underlying diseases is mandatory for an early treatment and therefore for a good prognosis

  28. MINDEN K, MINGELS A, NIEWERTH M, HEILIGENHAUS Aet GANSER G: [Juvenile Idiopathic Arthritis and Uveitis: Epidemiology Including Data from a National Database.], Klin.Monatsbl.Augenheilkd., Vol. 224(6), 469-472., 2007
    Organism:Deutsches Rheuma-Forschungszentrum Berlin, Chariteplatz 1, Berlin
    Abstract:    Uveitis is a potentially vision-threatening extra-articular manifestation of juvenile idiopathic arthritis (JIA) that manifests in approximately 13 % of all patients. According to the national ophthalmological and paediatric rheumatological database, one out of four children with JIA and uveitis develops ocular complications such as synechiae, band keratopathy, cataract, glaucoma and macula oedema. Independent risk factors of uveitis include the presence of a certain JIA subgroup, of antinuclear antibodies and age at onset. A late diagnosis, however, seems to be the relevant risk factor for uveitis complications in the course of the disease. The diagnosis of uveitis as early as possible is therefore the most important factor for a reduction of the morbidity of uveitis. Due to the usual lack of symptoms the diagnosis of uveitis requires, however, an examination by an ophthalmologist. This should be done immediately after the diagnosis of JIA and repeated in a risk-adapted manner during the follow-up

  29. NIEHUES T, WINTERHALTER S, ZIERHUT M, MICHELS H, BECKER MDet HEILIGENHAUS A: [EBM Analysis: Classic DMARDs (Disease-Modifying Antirheumatic Drugs) and Immunosuppressants in Arthritis and Uveitis.], Klin.Monatsbl.Augenheilkd., Vol. 224(6), 520-525., 2007
    Organism:Zentrum fur Kinder- und Jugendmedizin, Klinik fur Kinder-Onkologie, -Hamatologie und Klinische Immunologie, Padiatrische Immunologie und Rheumatologie, DusseldorfFAU - Niehues, T
    Abstract:    The best experience in the use of DMARDs/immunosuppressive drugs for treatment of juvenile idiopathic arthritis (JIA) and JIA-associated uveitis has been obtained with MTX. Controlled studies on the treatment of uveitis in JIA, however, are still lacking; this is also true for other DMARDs/immunosuppressive drugs. Thus, the grading of the evidence level for these substances only reaches evidence level III (expert opinion, clinical experience or descriptive studies). For the treatment of uveitis in JIA the utility of MTX in comparison to the new biological substance classes (e. g., tumor necrosis factor-alpha, blockers, interleukin-1 receptor antagonist) will have to be examined. Experience with Mycophenolate mofetil (MMF) in JIA uveitis is limited to single cases. According to data from a retrospective analysis cyclosporin A (CsA) appears to have a limited efficacy in JIA uveitis. The results with azathioprine are not consistent. Controlled studies which led to the approval of drugs for JIA are also mandatory for uveitis to offer the most effective and safe therapy for children

  30. NISTALA K, BABAR J, JOHNSON K, CAMPBELL-STOKES P, FOSTER K, RYDER Cet MCDONAGH JE: Clinical assessment and core outcome variables are poor predictors of hip arthritis diagnosed by MRI in juvenile idiopathic arthritis, Rheumatology (Oxford)., Vol. 46(4), 699-702., 2007
    Organism:Paediatric Rheumatology Department, Birmingham Children's Hospital, Steelhouse Lane, Birmingham B4 6NH, UK KNistala@ichuclacukFAU - Nistala, K
    Abstract:    OBJECTIVES: To compare the diagnostic performance of clinical assessment against magnetic resonance imaging (MRI) diagnosed hip arthritis in a juvenile idiopathic arthritis (JIA) population. To determine the clinical and serological predictors of MRI diagnosed hip arthritis. METHODS: A total of 34 JIA patients with established disease (mean disease duration 6.3 yrs) had their hip MRIs scored for features of active hip arthritis and hip damage. Results were compared with clinical variables (disease subtype, history of hip pain, core outcome variables (COV)) and the clinician's assessment of active hip arthritis. RESULTS: MRI features of active hip arthritis were found in 45 hips (70%) and hip damage in 36 hips (56%). Clinical assessment had fair agreement with MRI scoring of active arthritis in patients with disease duration <4 yrs (kappa score 0.38, P = 0.045). Clinical assessment had a sensitivity of 25.7% and specificity of 91% for detecting MRI diagnosed arthritis. Of the core outcome variables only erythrocyte sedimentation rate predicted inflammation detected on MRI (r = 0.44, P = 0.014). CONCLUSIONS: The association between the clinician's assessment, core outcome variables and MRI findings in this study was limited. This indicates that clinical and laboratory findings are inadequate diagnostic tools for the assessment of hip arthritis when compared with MRI as the gold standard

  31. OZYUREK AR, GURSES D, ULGER Z, LEVENT E, BAKILER ARet BERDELI A: Allelic frequency of the MCP-1 promoter -2518 polymorphism in the Turkish population and in Turkish patients with juvenile rheumatoid arthritis, Clin.Rheumatol., Vol. 26(4), 546-550., 2007
    Organism:Department of Pediatrics, Ege University Faculty of Medicine, Izmir, TurkeyFAU - Ozyurek, A Ruhi
    Abstract:    Although genetic and environmental factors contribute to the pathogenesis of juvenile rheumathoid arthritis (JRA), the etiology and pathogenesis remain controversial. The objective of this study was to investigate genotypic and allelic frequencies of monocyte chemoattractant protein-1 (MCP-1) gene -2518 (G/A) polymorphism in the healthy Turkish population and patients with JRA. Genomic DNA was collected from 66 JRA patients and 150 healthy individuals. To evaluate the association of the -2518 (G/A) MCP-1 gene polymorphism with the outcome of JRA, we analyzed the types of JRA and the score on the childhood health assessment questionnaire (C-HAQ score). In the healthy Turkish population, the frequencies of A and G alleles were 71 and 29%, respectively. No significant difference was observed between the JRA patients and healthy subjects in the distribution allelic and genotypic frequencies of the -2518 (G/A) MCP-1 gene polymorphism (p>0.05). However, the AG genotype was found to be higher and the AA genotype was found to be lower in the patients with systemic type JRA compared to those with the other types of JRA (p=0.019). When the JRA patients were evaluated according to the C-HAQ score, we found that the -2518 (G/A) MCP-1 gene polymorphism did not relate the prognosis (p>0.05). AG genotype was found to be higher in the systemic type of JRA. The results indicate that MCP-1 gene polymorphism might slightly associate with patients with systemic JRA. Further studies are needed to elucidate the role of this polymorphism in the pathogenesis of JRA in various populations because this polymorphism has a functional significance and an ethnic difference

  32. PAMUK ON, PAMUK GE, USTA Uet CAKIR N: Hemophagocytic syndrome in one patient with adult-onset Still's disease. Presentation with febrile neutropenia, Clin.Rheumatol., Vol. 26(5), 797-800., 2007
    Organism:Department of Rheumatology, Trakya University Medical Faculty, Edirne, Turkey omernpamuk@yahoocomFAU - Pamuk, Omer Nuri
    Abstract:    Macrophage activation syndrome (MAS) is an important complication seen in systemic for juvenile rheumatoid arthritis; until now, it has been reported in only a few cases of adult-onset Still's disease (AOSD). Here, we shall present a 50-year-old female patient who was using steroids and antimalarial drugs for AOSD, and who developed MAS during follow-up. The patient presented with febrile neutropenia, and the neutropenic period lasted for 15 days. The examination of bone marrow aspiration smears demonstrated increased macrophages and findings of hemophagocytosis. Flow cytometric analysis of peripheral blood showed decreased natural killer cells. The patient developed neurologic findings during this period, and during the recovery of neutropenia, she had icterus and liver function test abnormalities. The patient was given granulocyte colony-stimulating factor during neutropenic period, and her neutropenia improved after the administration of high-dose steroids. Our patient was the first AOSD patient who presented with febrile neutropenia during the course of her disease and who was diagnosed to have MAS

  33. PEDERSEN M, JACOBSEN S, GARRED P, MADSEN HO, KLARLUND M, SVEJGAARD A, PEDERSEN BV, WOHLFAHRT Jet FRISCH M: Strong combined gene-environment effects in anti-cyclic citrullinated peptide-positive rheumatoid arthritis: a nationwide case-control study in Denmark, Arthritis Rheum., Vol. 56(5), 1446-1453., 2007
    Organism:Danish Epidemiology Science Centre, Statens Serum Institut, Copenhagen, Denmark mtb@ssidkFAU - Pedersen, Merete
    Abstract:    OBJECTIVE: To study the role of shared epitope (SE) susceptibility genes, alone and in combination with tobacco smoking and other environmental risk factors, for risk of subtypes of rheumatoid arthritis (RA) defined by the presence or absence of serum antibodies against cyclic citrullinated peptides (CCPs). METHODS: To address these issues, a nationwide case-control study was conducted in Denmark during 2002-2004, comprising incident cases of RA or patients with recently diagnosed RA (309 seropositive and 136 seronegative for IgG antibodies against CCP) and 533 sex- and age-matched population controls. Associations were evaluated by logistic regression analyses, in which odds ratios (ORs) served as measures of relative risk. RESULTS: Compared with individuals without SE susceptibility genes, SE homozygotes had an elevated risk of anti-CCP-positive RA (OR 17.8, 95% confidence interval [95% CI] 10.8-29.4) but not anti-CCP-negative RA (OR 1.07, 95% CI 0.53-2.18). Strong combined gene-environment effects were observed, with markedly increased risks of anti-CCP-positive RA in SE homozygotes who were heavy smokers (OR 52.6, 95% CI 18.0-154), heavy coffee drinkers (OR 53.3, 95% CI 15.5-183), or oral contraceptive users (OR 44.6, 95% CI 15.2-131) compared with SE noncarriers who were not exposed to these environmental risk factors. CONCLUSION: Persons who are homozygous for SE susceptibility genes, notably those who are also exposed to environmental risk factors, have a markedly and selectively increased risk of anti-CCP-positive RA. A distinction between anti-CCP-positive RA and anti-CCP-negative RA seems warranted, because these RA subtypes most likely represent etiologically distinct disease entities

  34. RAPOFF MAet LINDSLEY CB: Improving adherence to medical regimens for juvenile rheumatoid arthritis, Pediatr.Rheumatol.Online.J., Vol. 5, 10, 2007
    Organism:Department of Pediatrics, University of Kansas Medical Center, Kansas City, Kansas, USA mrapoff@kumceduFAU - Rapoff, Michael A
    Abstract:    ABSTRACT: Poor adherence to medical regimens can compromise the efficacy of treatments for children and adolescents with juvenile rheumatoid arthritis (JRA). The purpose of this review is to describe medical regimens for the treatment of JRA and the rates of adherence to these regimens. We also summarize and critically the few research studies aimed at improving adherence to regimens for JRA. Finally, we summarize strategies for enhancing adherence in clinical practice

  35. ROUX CH, BROCQ O, BREUIL V, ALBERT Cet EULLER-ZIEGLER L: Pregnancy in rheumatology patients exposed to anti-tumour necrosis factor (TNF)-alpha therapy, Rheumatology (Oxford)., Vol. 46(4), 695-698., 2007
    Organism:Rheumatology Department, University Hospital, Nice, France roux101fr@yahoofrFAU - Roux, C H
    Abstract:    OBJECTIVES: Anti-tumour necrosis factor (TNF)-alpha therapies are considered category B drugs for pregnancy. Although sometimes prescribed to women of reproductive age, data in humans are limited with regard to safety for a developing fetus. The objectives of the present article are to report experience of anti-TNF-alpha use in pregnancy, and review the international literature. METHODS: Since 1999 the present authors have used anti-TNF-alpha (infliximab, etanercept, adalimumab) to treat patients with various chronic rheumatic conditions. All patients were prospectively followed during their treatment time and data were systematically collected. RESULTS: In a group of 442 patients treated with anti-TNF, three women with RA unexpectedly became pregnant One treated with etanercept chose a therapeutic termination at two and a half months, despite of any ultrasound anomaly, and satisfactory fetal growth. The other two patients (one with adalimumab exposure and one with etanercept exposure) delivered healthy infants. The following perinatal complications were observed: prematurity, neonatal jaundice, neonatal urinary Escherichia coli infection and adrenal congenital hyperplasia of probable hereditary origin. CONCLUSIONS: To date, there is no evidence that TNF-alpha antagonists are associated with embryo toxicity, teratogenicity or increased pregnancy loss. However, caution should be taken when anti-TNF agents are used during pregnancy, as human experience is still extremely limited, particularly in patients with rheumatic diseases among whom there are several alarming reports. The potential risk should be balanced against the known risks associated with DMARDs and steroid therapy. Large registries will be necessary before firm conclusions can be drawn

  36. SHARMA SM, RAMANAN AV, RILEY Pet DICK AD: Use of infliximab in juvenile onset rheumatological disease-associated refractory uveitis: efficacy in joint and ocular disease, Ann.Rheum.Dis., Vol. 66(6), 840-841., 2007
    Organism:

  37. SHAW KL, SOUTHWOOD TRet MCDONAGH JE: Development and preliminary validation of the 'Mind the Gap' scale to assess satisfaction with transitional health care among adolescents with juvenile idiopathic arthritis, Child Care Health Dev., Vol. 33(4), 380-388., 2007
    Organism:Institute of Child Health, University of Birmingham, Birmingham, UKFAU - Shaw, K L
    Abstract:    Background To develop a scale to assess satisfaction with transitional health care among adolescents with a chronic illness and their parents. Methods The 'Mind the Gap' scale was developed using evidence from a previous needs assessment, in three stages: (1) definition of the construct; (2) design of the scale items, response options and instructions; (3) full administration of the scale, item analysis and dimensionality analysis. The scale was administered to 308 adolescents with juvenile idiopathic arthritis (JIA) and 303 parents/guardians, prior to and 12 months after the implementation of an evaluation of a structured and co-ordinated programme of transitional care. The patient population involved adolescents with JIA and their parents recruited from 10 major UK rheumatology centres. Results A total of 301 (97.7%) adolescents and 286 (95.0%) parents chose to complete the questionnaire, with median item completion rates of 100.0% (0-100%) for both adolescents and parents thus confirming feasibility. Face and content validity were confirmed. Factor analyses revealed a three-factor structure which explained 49.5% and 56.1% of the variation in adolescent and parent scores respectively. The internal consistency of each subscale ('management of environment', 'provider characteristics' and 'process issues') was indicated by Cronbach's alphas of 0.71, 0.89 and 0.89 for adolescents, respectively, and 0.83, 0.91 and 0.92 for parents respectively. Cronbach's alphas for the entire scales were 0.91 and 0.94 for the adolescent and parent forms respectively. Conclusion These preliminary results report the potential of the 'Mind the Gap' scale in evaluating transitional care for adolescents with JIA. In view of the generic nature of transitional care reflected in the scale, this scale has wider potential for use with adolescents with other chronic illness in view of the generic nature of transition. This development is particularly timely in the context of transitional care developments in the UK and further validation of the scale is in progress

  38. SHAW KL, SOUTHWOOD TRet MCDONAGH JE: Young people's satisfaction of transitional care in adolescent rheumatology in the UK, Child Care Health Dev., Vol. 33(4), 368-379., 2007
    Organism:Institute of Child Health, University of Birmingham, Birmingham, UKFAU - Shaw, K L
    Abstract:    Background To examine the quality of transitional health care from the perspectives of young people with juvenile idiopathic arthritis (JIA) and their parents. Methods Adolescents with JIA and their parents were recruited from 10 major UK rheumatology centres. Satisfaction with health-care delivery was measured prior to, and 12 months after, the implementation of a structured and co-ordinated programme of transitional care using self-completed questionnaires designed for this study. Results Of 359 families invited to participate, 308 (86%) adolescents with JIA and 303 (84%) parents/guardians accepted. A fifth of adolescents had persistent oligoarthritis. Median age was 14.2 (11-18) years with median disease duration of 5.7 (0-16) years. Young people and their parents rated provider characteristics more important than aspects of the physical environment or process issues. Staff honesty and knowledge were rated as the most essential aspects of best practice. Prior to implementing the programme of transitional care, parents rated service delivery for all items significantly worse than best practice. Overall satisfaction improved 12 months after entering the programme. However, while parent satisfaction improved for 70.4% of items, significant improvements were only observed for three (13.6%) items rated by adolescents. Conclusion The perceived quality of health care for young people with JIA and their parents was significantly lower than what they would like. Satisfaction with many aspects of care during transition from paediatric to adult services can be improved through the implementation of a structured, co-ordinated programme of transitional care

  39. SIMON F, PAROLA P, GRANDADAM M, FOURCADE S, OLIVER M, BROUQUI P, HANCE P, KRAEMER P, MOHAMED AA, DE L, X, CHARREL Ret TOLOU H: Chikungunya infection: an emerging rheumatism among travelers returned from Indian Ocean islands. Report of 47 cases, Medicine (Baltimore)., Vol. 86(3), 123-137., 2007
    Organism:From Service de Pathologie Infectieuse et Tropicale, Hopital d'Instruction des Armees Laveran, Marseilles, France simon-f@wanadoofrFAU - Simon, Fabrice
    Abstract:    A large chikungunya virus (CHIKV) outbreak emerged in 2005-2006 in the Indian Ocean islands, including Comoros, Mayotte, Mauritius, the Seychelles, and particularly in Reunion Island where 35% of 770,000 inhabitants were infected in 6 months. More recently, circulation of the virus has been documented in Madagascar and in India where CHIKV is spreading rapidly. CHIKV-infected visitors have returned home to nonendemic regions from these islands. We conducted a 14-month prospective observational study on the clinical aspects of CHIKV infection imported to Marseilles, France, in travelers returning from the Indian Ocean islands. A total of 47 patients have been diagnosed with imported CHIKV infection confirmed by serology, reverse transcription-polymerase chain reaction, and/or viral culture. At the early stage of the disease (within 10 days of the disease onset), fever was present in 45 of 47 patients. A rash was present in the first week in 25 cases. All patients suffered with arthritis. The most frequently affected joints were fingers, wrists, toes, and ankles. Eight patients were hospitalized during the acute stage, including 2 severe life-threatening cases. A total of 38 patients remained symptomatic after the tenth day with chronic peripheral rheumatism, characterized by severe joint pain and multiple tenosynovitis, with a dramatically limited ability to ambulate and carry out activities in daily life. Three patients were hospitalized at this stage for severe persistent handicap. Follow-up demonstrated slow improvement in joint pain and stiffness despite symptomatic treatment, mainly antiinflammatory and analgesic drugs. In the current series we describe 2 stages of the disease, an initial severe febrile and eruptive polyarthritis, followed by disabling peripheral rheumatism that can persist for months. We point out the possibility of transitory peripheral vascular disorders during the second stage and the occasional benefit of short-term corticosteroids. As CHIKV could spread throughout the world, all physicians should be prepared to encounter this arboviral infection

  40. TERRONES-MUNOZ V, MELOT C, GANGJI V, STEINFELD Set APPELBOOM T: Course of juvenile rheumatoid arthritis: social life is less affected than school functioning, physical activity, and well-being during a follow-up of 1.5-13 years, Eur.J.Pediatr., Vol. 165(6), 427-428., 2006
    Organism:Hopital Erasme, Universite Libre de Bruxelles, Brussels, BelgiumFAU - Terrones-Munoz, V
    Abstract:

  41. TLUSTOCHOWICZ M: [Cyclosporine combined with another basic drug for the management of rheumatoid arthritis], Ann.Acad.Med.Stetin., Vol. 52 Suppl 2, 23-27., 2006
    Organism:Klinika Chorob Wewnetrznych i Reumatologii Wojskowego Instytutu Medycznego CSK MON w Warszawie ul Szaserow 128, 00-909 WarszawaFAU - Tlustochowicz, Malgorzata
    Abstract:    The aim of this study was to assess the efficacy of combined treatment with cyclosporine A and another disease-modifying anti-rheumatic drug in patients with monotherapy-resistant rheumatoid arthritis, to find the minimal effective doses of combined drugs, to determine the frequency and type of side-effects, and to analyze causes for drug withdrawal. The study was performed in two groups of rheumatoid arthritis patients diagnosed according to ACR criteria who presented with symptoms of active inflammatory disease in spite of six-month-long treatment with full dose of at least one drug. Patients previously treated with cyclosporine A, with poorly controlled hypertension, and kidney failure were excluded from the study. At the beginning of the study, all patients were on 15 mg prednizone and 1-3 basic drugs. In group I (n = 36 patients), monotherapy was combined with an increasing dose of cyclosporine A (from 1.5-2 to the maximal dose of 5 mg/kg/day). Disease activity was determined according to modified ACR criteria. Improvement was observed in 30 patients (83.3%). Improvement was significant in 5 patients (13.9%), moderate in 11 (30.5%), and slight in 14 (38.9%). No improvement was observed in 6 patients (16.7%). The effective dose was 100-400 mg/day (mean 180.5 mg/day or 2,5-3,0 mg/kg/day). Treatment was terminated in 72.2% of patients, mostly because of side-effects (36.1%). In 16.7% of patients, the cause for termination was lack of early improvement or late recurrence. In group II (n = 11 patients), leflunomide 20 mg/day was added to the previous treatment. Disease activity was estimated according to DAS 28 scale. Combined treatment with cyclosporine A and leflunomide was effective in 43.3% of patients. It was demonstrated that cyclosporine A in combination therapy may cause improvement in patients resistant to other basic drugs. Its effective dose is approx. 2.5-3.0 mg/kg/day. Side-effects requiring drug withdrawal were present in one-fourth of patients and together with non-effective therapy were the most common cause for drug withdrawal. However, it must be emphasized that patients who were qualified to this study had a severe course of the disease resistant to other therapies. In this context, our combination therapy deserves attention

  42. UNSAL E, ARLI AOet AKMAN H: Rhupus arthropathy as the presenting manifestation in Juvenile SLE: a case report, Pediatr.Rheumatol.Online.J., Vol. 5(1), 7, 2007
    Organism:Dokuz Eylul University, Faculty of Medicine, Department of Pediatrics, Division of Immunology-Rheumatology, Balcova 35340 Izmir, Turkiye erbilunsal@deuedutr
    Abstract:    ABSTRACT: An 8.5-year-old girl was referred with swelling of both knees lasting for two years. ANA was found as negative. She was diagnosed as oligoarticular JIA. After two years of follow-up, thrombocytopenia was detected during routine screening. Her ANA and anti ds-DNA antibodies also became positive, with low levels of C3 and C4. She was diagnosed as Juvenile SLE, meeting the criteria cytopenia, positive immunoserology (anti dsDNA), positive ANA test, and four years of ongoing chronic arthritis, so called as "rhupus arthropathy". We should be aware of the several initial incomplete presentations of lupus in children. We should be careful in monitoring the serious manifestations of the disease in juvenile lupus patients with rhupus arthropathy, and consider the poor response to standard disease modifying agents

  43. YU L, WANG LD, LU DC, ZHANG WG, QI ZM, ZHANG YFet WANG H: [Arthroscopic assisted diagnosis and treatment of knee extension limitation], Zhonghua Wai Ke.Za Zhi., Vol. 44(12), 833-835., 2006
    Organism:Department of Orthopaedics, First Hospital, Dalian Medical University, Dalian 116021, China dl_yuli@163comFAU - Yu, Li
    Abstract:    OBJECTIVE: To figure out the incidence and etiology of knee extension limitation and then to find out the proper methods of arthroscopic assisted diagnosis and treatment. METHODS: We reviewed 303 cases of arthroscopic assisted operation from January to October 2003, 95 cases of which suffered from knee extension limitation before operation, including 54 male and 41female and the mean age was 36.2 years old. The direct reasons of knee extension limitation were identified by routine arthroscopic examination and operations were carried out according to results of the examination. RESULTS: Incidence of knee extension limitation in this group of patients was 31.4%. Trauma, mainly meniscus and ligament injury accounted for 67.4%, which was the most common reason of knee extension limitation. Acute or chronic arthritis like degenerative arthritis, non-specific synovitis, synovial chondromatosis, rheumatoid arthritis, pigmented villonodular synovitis, gouty arthritis and acute pyogenic arthritis formed another common reason. The follow-up period ranged from 3 to 20 months, average 13.3 months. 82 cases gained full extension immediately after operation, 9 cases gained full extension after 3 weeks rehabilitation post-operation, 4 cases did not gain full extension 1 year after operation, recurrence was observed in 4 cases. CONCLUSIONS: Arthroscopy is the best method for diagnosis of knee extension limitation at present. Satisfactory results can be expected after early arthroscopic assisted treatment