Bibliography March 06

1. AL MAYOUF SM, MADI SM, ALMANE K, AL JUMMAH S: Comparison of clinical and laboratory variables in familial versus sporadic systemic onset juvenile idiopathic arthritis. J Rheumatol 33:3 597-600, 2006
   Organism: Department of Pediatrics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia mayouf@kfshrcedusaFAU - Al-Mayouf, Sulaiman M
   Abstract: OBJECTIVE: To compare patients with familial versus sporadic juvenile idiopathic arthritis (JIA) with respect to clinical and laboratory variables. METHODS: The familial JIA group comprised 11 affected siblings belonging to 4 families, while the comparative group comprised 22 patients selected by systematic sampling from JIA patients presenting to our pediatric rheumatology clinic; the first patient was chosen randomly and the subsequent patients chosen at intervals of 3. The 2 groups were compared with respect to demographic information, age at onset of disease, disease activity, disease damage, and laboratory variables. RESULTS: The 2 groups were comparable with respect to age, sex, and onset type of disease. All patients from the familial group were from a southern province of Saudi Arabia (p = 0.001). The familial group had an earlier age at onset of disease (p = 0.039), the mean number of actively inflamed joints was higher (p = 0.009), and functional capacity as measured by Childhood HAQ was worse (p = 0.048), compared with the sporadic group. Other variables showed no significant differences. CONCLUSION: The comparison of patients with familial versus sporadic JIA revealed a significant difference in origin of patients and age at onset of disease. These differences may be helpful in identifying the predisposing genes in familial patients with JIA

2. BAECKLUND E, ILIADOU A, ASKLING J, EKBOM A, BACKLIN C, GRANATH F, CATRINA AI, ROSENQUIST R, FELTELIUS N, SUNDSTROM C, KLARESKOG L: Association of chronic inflammation, not its treatment, with increased lymphoma risk in rheumatoid arthritis. Arthritis Rheum 54:3 692-701, 2006
   Organism: Department of Rheumatology, Akademiska Hospital, Uppsala, Sweden EvaBaecklund@swipnetseFAU - Baecklund, Eva
   Abstract: OBJECTIVE: Chronic inflammatory conditions such as rheumatoid arthritis (RA) have been associated with malignant lymphomas. This study was undertaken to investigate which patients are at highest risk, and whether antirheumatic treatment is hazardous or protective. METHODS: We performed a matched case-control study of 378 consecutive Swedish RA patients in whom malignant lymphoma occurred between 1964 and 1995 (from a population-based RA cohort of 74,651 RA patients), and 378 controls. Information on disease characteristics and treatment from onset of RA until lymphoma diagnosis was abstracted from medical records. Lymphoma specimens were reclassified and tested for Epstein-Barr virus (EBV). Relative risks (odds ratios [ORs]) for lymphomas (by subtype) associated with deciles of cumulative disease activity were assessed, as were ORs associated with drug treatments. RESULTS: The relative risks of lymphoma were only modestly elevated up to the seventh decile of cumulative disease activity. Thereafter, the relative risk increased dramatically (OR ninth decile 9.4 [95% confidence interval 3.1-28.0], OR tenth decile 61.6 [95% confidence interval 21.0-181.0]). Most lymphomas (48%) were of the diffuse large B cell type, but other lymphoma subtypes also displayed an association with cumulative disease activity. Standard nonbiologic treatments did not increase lymphoma risk. EBV was present in 12% of lymphomas. CONCLUSION: Risk of lymphoma is substantially increased in a subset of patients with RA, those with very severe disease. High inflammatory activity, rather than its treatment, is a major risk determinant

3. CAO LF, LU YM, MA M, XUE HY, ZHAO Y, YU HQ, MAO HY, GU YY: [Levels of serum interleukin-15 and the expression of T-helper lymphocyte subsets in peripheral blood of children with juvenile rheumatoid arthritis.]. Zhongguo Dang Dai Er Ke Za Zhi 8:1 9-12, 2006
   Organism: Department of Pediatrics, Renji Hospital, Shanghai Second Medical University, Shanghai 200001, China clf530417@yahoocomcnFAU - Cao, Lan-Fang
   Abstract: OBJECTIVE: To study the changes of serum interleukin-15 (IL-15) levels and the expression of CD4(+)T (T-helper lymphocyte) subsets CD4(+)CD45RA(+) and CD4(+)CD45RO(+) in peripheral blood of children with juvenile rheumatoid arthritis (JRA). METHODS: The serum concentration of IL-15 was detected using ELISA in 39 children with JRA. The expressions of CD4(+)CD45RA(+)T and CD4(+)CD45RO(+)T in peripheral blood were detected by flow cytometry in 24 out of the 39 patients with JRA. Twenty-six age and sex-matched healthy children were used as the Control group. RESULTS: The mean serum IL-15 level in JRA patients was significantly higher than that in controls (1.37 +/- 0.98 pg/mL vs 0.96 +/- 0.41 pg/mL, P <0.05). Among the 39 JRA patients, the serum IL-15 level in 17 patients with systemic JRA increased remarkably (P < 0.01), but not in patients with the other two types of JRA, the oligoarthritis and polyarthritis (n=13, n=9, respectively), compared with that in controls. The mean serum IL-15 level of the JRA patients was significantly reduced after conventional treatment (P < 0.01). The serum IL-15 level in JRA patients positively correlated with white blood cell count (r=0.347, P <0.05) and C reactive protein (r=0.452, P < 0.01)but not with the erythrocyte sedimentation rate. The patients with high serum IL-15 levels (>/= medium level 1.73 pg/mL) had higher expression of CD4(+)CD45RO(+)T than those with low serum IL-15 levels (< medium level)(16.29 +/- 5.46% vs 11.75 +/- 3.15 %, P < 0.05). CONCLUSIONS: The serum IL-15 levels in JRA patients increased significantly. An increased IL-15 level can transform CD45RA into CD45RO in peripheral blood of patients with JRA, and then result in T lymphocyte activation and mediate the immunopathological impairment. IL-15 may be used a marker for the evaluation of severity of JRA

4. CUNHA BA, PARCHURI S, MOHAN S: Fever of unknown origin: temporal arteritis presenting with persistent cough and elevated serum ferritin levels. Heart Lung 35:2 112-116, 2006
   Organism: Infectious Disease Division, Winthrop-University Hospital, Mineola, New York 11501, USAFAU - Cunha, Burke A
   Abstract: BACKGROUND: Fever of unknown origin (FUO) at the present time is most frequently caused by neoplasm and less commonly by infection. Currently, collagen vascular diseases (CVDs) are an uncommon cause of FUO because most are readily diagnosable by serologic methods and do not remain undiagnosed for sufficient time to present as FUOs. CVDs presenting as FUOs not readily diagnosable with specific tests include late-onset rheumatoid arthritis, adult juvenile rheumatoid arthritis, and polymyalgia rheumatica/temporal arteritis (TA). TA, or giant cell arteritis, is an uncommon arteritis of the mid- and large-sized extracranial arteries of the head and neck and is a rare cause of FUO. TA is characterized by headache, scalp tenderness, jaw pain on chewing, and sudden loss of vision. Fever, anorexia, weight loss, and night sweats may also be present. With TA, respiratory symptoms occur in 9% and are the presenting feature in 4%. Laboratory abnormalities associated with TA include a highly elevated erythrocyte sedimentation rate, anemia, and thrombocytosis, and mildly increased alkaline phosphatase/serum transaminases. PATIENT: We present a patient with FUO caused by TA whose predominant presenting symptom was persistent cough that overshadowed head and neck symptoms of TA. To the best of our knowledge, this is the first case of TA presenting as an FUO, with a highly elevated serum ferritin level. RESULTS: We conclude that highly elevated serum ferritin levels in patients with FUO should alert the clinician to consider TA in the differential diagnosis

5. DAVIES K, COPEMAN A: The spectrum of paediatric and adolescent rheumatology. Best Practice and Research in Clinical Rheumatology (United Kingdom ), 20/2 (179-200) 20:2 179-200, 2006
   Abstract: A wide range of conditions comes under the umbrella of paediatric rheumatology. These problems are common in childhood and cover a wide variety of presentations and outcomes. Many conditions are benign and self-limiting, others run a chronic relapsing and remitting course; some are fatal. Broadly, rheumatological problems can be subdivided into inflammatory, mechanical, and behaviourally or psychologically driven aetiologies, although these are not mutually exclusive. The majority of patients with rheumatological conditions will present with symptoms that are easily localized to the musculoskeletal system. Sometimes, however, a child with a rheumatological condition may present less specifically: For example with fatigue, deterioration in school performance or growth retardation. In this case a rheumatological aetiology may be overlooked unless it is specifically suspected and a careful assessment for musculoskeletal symptoms and signs is undertaken. In order to arrive at the correct diagnosis and plan appropriate further management, it is therefore important for the clinician both to have an effective system to ensure that musculoskeletal symptoms are appropriately determined and assessed, and to be aware of the wide range of conditions, which can cause such symptoms in childhood and adolescence. The keys to this lie in acquiri ng the clinical skills necessary to accurately assess such patients and awareness of the changing differential diagnosis with the age of the child. In this chapter, we aim to address these issues, initially by discussing the prevalence of musculoskeletal symptoms in children and adolescents and the various conditions which cause them, and subsequently by looking at common presentations of rheumatic disease in childhood and suggesting an approach to diagnosis in each case. (c) 2005 Elsevier Ltd. All rights reserved

6. DAVIS PJC, MCDONAGH JE: Principles of management of musculoskeletal conditions in children and young people. Best Practice and Research in Clinical Rheumatology (United Kingdom ), 20/2 (263-278) 20:2 263-278, 2006
   Abstract: Musculoskeletal symptoms and rheumatic conditions are common throughout childhood and adolescence. Age- and development-appropriate care and management of children and young people with such conditions is vital, acknowledging that they are NOT small adults! The major aspect of both paediatric and adolescent rheumatology care which differentiates it from adult care is the fact that children and young people are still growing, in contrast to the ageing and senescence which characterizes adult rheumatology. Growth must be considered in the global sense, incorporating cognitive and psychosocial growth as well as physical growth. Likewise, the reciprocal influences of growth and a chronic rheumatic condition should be considered when caring for young people with childhood-onset rheumatic disease. This chapter will detail the general principles of management of such symptomatology with primary reference to chronic conditions. (c) 2005 Elsevier Ltd. All rights reserved

7. DORIA AS, BABYN PS, FELDMAN B: A critical appraisal of radiographic scoring systems for assessment of juvenile idiopathic arthritis. Pediatr Radiol .: 2006
   Organism: Department of Diagnostic Imaging, The Hospital for Sick Children, 555 University Ave, Toronto, Ontario, M5G 1X8, Canada
   Abstract: Assessing structural damage to joints over time is essential for evaluating the effectiveness of therapeutic interventions for patients with inflammatory arthritis. Although radiography is able to quantify joint damage, the changes found with conventional radiography early in the disease course are nonspecific, and late radiographic changes are often irreversible. Although many clinical trials on drug development for children still use radiographic scales as endpoints for the study, more specific therapies have been developed for juvenile idiopathic arthritis (JIA) that would enable imaging to "fine-tune" patients to placement into specific treatment algorithms. As a result, new imaging scales to identify early abnormalities are clearly needed. Many pediatric rheumatology centers around the world persistently apply adult-designed radiographic scoring systems to evaluate the progression of JIA. Few pediatric-targeted radiographic scales are available for assessment of progression of JIA in growing joints, and the clinimetric and psychometric properties of such scales have been poorly investigated. We present a critique to the evaluative, discriminative, and predictive roles of the van der Heijde modification of Sharp's radiographic method, a scale originally designed to assess damage to joints of adults with rheumatoid arthritis, when it is applied to a pediatric population. We discuss the advantages and drawbacks of this radiographic scoring system for assessing growing joints and the ability of MRI to overcome inadequacies of conventional radiography

8. FABER C, MORBACH H, SINGH SK, GIRSCHICK HJ: Differential expression patterns of Recombination Activating Genes in individual mature B cells in Juvenile Idiopathic Arthritis. Ann Rheum Dis .: 2006
   Organism: University of Wurzburg, Deptof Pediatrics, Section of Pediatric Rheumatology, Germany
   Abstract: OBJECTIVE: Re-expression of recombination activating genes (RAG) in peripheral B cells might be of relevance in the development of autoreactive antibodies in autoimmune diseases. The presence of antinuclear antibodies as a hallmark of oligoarticular juvenile idiopathic arthritis (o-JIA, early onset type) is indicative for a break down in immunological tolerance. Therefore we examined the expression of RAG genes in peripheral blood mature B lymphocytes in patients with o- JIA. METHODS: We examined 777 individual peripheral blood CD19+CD27+CD5+ / CD5?memory B cells, isolated from three ANA+ o-JIA patients and three healthy age-matched children for the expression of RAG1 and RAG2 mRNA. Furthermore, we searched for mRNA transcripts of activation-induced cytidine deaminase (AID) and IgG to further determine their developmental stage. RESULTS: We found mRNA for any of the two RAG genes in B cells of JIA and controls. However, the predominance of RAG1 or RAG2 was different. A significantly decreased frequency of RAG2 expressing memory B cells in both CD5+ and CD5?populations was noted in JIA (p<0,001), whereas the number of RAG1 expressing B cells was slightly increased. Coordinate expression of both the RAG genes was a rare event, similar in the CD5+ populations (1% in controls, 2% in JIA), but different among the CD5?compartments (5%, 0% resp. ; p<0,01). CONCLUSION: These results argue for a reduced coordinate RAG expression in peripheral CD5?memory B cells of o-JIA. Thus, we hypothesize that impaired receptor revision could contribute to autoimmune pathogenesis in JIA

9. FOSTER HE, CABRAL DA: Is musculoskeletal history and examination so different in paediatrics? Best Pract Res Clin Rheumatol 20:2 241-262, 2006
   Organism: Musculoskeletal Research Group, Medical School, University of Newcastle, Framlington Place, Catherine Cookson Building, NE2 4HH Newcastle, UK hefoster@nclacukFAU - Foster, Helen E
   Abstract: Musculoskeletal (MSK) complaints in children and adolescents are common. The differential diagnosis is broad and based predominantly on clinical assessment. The skills both for eliciting history and for examination require understanding of the child/young person's specific emotional and cognitive developmental stage; interpretation of the findings requires knowledge of normal (and abnormal) motor and musculoskeletal growth and development. We specifically describe the different approach, unique skills and knowledge required by all clinicians who assess children and adolescents with MSK complaints; children and adolescents are not 'just little adults'. We emphasize the importance of clinical competence in ensuring that patients with juvenile idiopathic arthritis are diagnosed early and referral to specialist centres is not delayed with consequential suboptimal management and outcome. There is evidence that physician clinical skills in MSK assessment are inadequate, probably as a result of systemic deficiencies in the education process. Current and proposed solutions are discussed

10. HAFNER R: Juvenile idiopathic arthritis. An old disease with a new name
    DIE JUVENILE IDIOPATHISCHE ARTHRITIS. EIN ALTES KRANKHEITSBILD MIT NEUEM NAMEN. Padiatrische Praxis (Germany ) 68:1 127-148, 2006
    Abstract: For chronic childhood arthritis a new nomenclature and classification has been introduced. The diagnosis juvenile idiopathic arthritis is divided into 7 categories. They all have in common the symptom arthritis which is characterized by joint swelling, functional impairment and pain. An oligoarticular joint pattern with not more than 4 joints involved is differentiated from polyarthritis. Tenosynovitis and synovial cysts can be observed. Arthritis results in pain relieving malpositions of the affected joints, and especially in small children local growth disturbances develop. Growth in height is reduced in highly active, especially in systemic forms. These children have fever, rash and inner organ involvement. They are at risk to develop amyloidosis or a macrophage activation syndrome. Chronic uveitis can occur in up to half of the children with oligoarthritis. Laboratory data and imaging procedures are important for diagnosis and follow-up, however, they must always be evaluated together with the clinical picture. Treatment compr ises drug therapy including intraarticular injections, individual physiotherapy together with occupational therapy and adjustment of devices as well as a psychosocial care

11. HOFER M: Spondylarthropathies in children--are they different from those in adults? Best Pract Res Clin Rheumatol 20:2 315-328, 2006
    Organism: Centre Multisite Romand de Rhumatologie Pediatrique, Department of Paediatrics, University of Lausanne, Lausanne and University of Geneva, Geneva, Switzerland michaelhofer@chuvchFAU - Hofer, Michael
    Abstract: Juvenile spondylarthropathies (JSpAs) comprise a group of rheumatic diseases distinct from other categories of juvenile arthritis. Several classification systems have been applied, and some are specific for children, such as the seronegative enthesopathy and arthropathy (SEA) syndrome and the enthesitis-related arthritis, diagnostic forms in the International League of Associations for Rheumatism (ILAR) classification. JSpA seems more frequent than was previously believed, but actual epidemiological data show important variations between studies. Compared to adult patients, children with JSpA present with peripheral arthritis and enthesitis early in disease but sacroiliac and spine joints involvement many years later. A multidisciplinary team in a paediatric environment should be responsible for the management of children with spondylarthropathies to ensure the best care for these children with their chronic disease and risk of long-term disability. Recent advances in the treatment of rheumatic diseases with biological agents show promising results in children with JSpA. Further research needs to be conducted to increase our knowledge of the long-term outcome of these patients, to improve management, and to prevent long-term consequences of the disease

12. KAHN P, WEISS M, IMUNDO LF, LEVY DM: Favorable Response to High-Dose Infliximab for Refractory Childhood Uveitis. Ophthalmology .: 2006
    Organism: Morgan Stanley Children's Hospital of New York-Presbyterian, Columbia University Medical Center, New York, New York
    Abstract: OBJECTIVE: Uveitis in children most commonly is associated with juvenile idiopathic arthritis. In addition to topical glucocorticoids, treatment may include systemic immunosuppressive agents. Tumor necrosis factor alpha (TNF-alpha) has been implicated in the pathogenesis of uveitis; therefore, TNF-alpha blockade seems to be a reasonable therapeutic option to investigate. We report successful treatment of children with uveitis using infliximab. STUDY DESIGN: A retrospective study of our complete experience using infliximab for the treatment of childhood uveitis was conducted. PARTICIPANTS: Seventeen children (14 females, 3 males) with chronic uveitis were administered high-dose infliximab (10-20 mg/kg/dose). MAIN OUTCOME MEASURES: Our main outcome measure was the ability to eliminate all signs of intraocular inflammation. RESULTS: All 17 patients demonstrated a dramatic, rapid response, with no observed inflammation in 13 patients after the second infusion, and 4 patients requiring 3 to 7 infusions to achieve disease quiescence. Additional immunosuppressives and topical glucocorticoids were tapered when patients achieved no intraocular inflammation. CONCLUSIONS: In this series, high-dose infliximab was a rapidly effective, well-tolerated therapeutic agent for the treatment of chronic, medically refractory, noninfectious uveitis

13. KONTTINEN L, KANKAANPAA E, LUOSUJARVI R, BLAFIELD H, VUORI K, HAKALA M, RANTALAIHO V, SAVOLAINEN E, UUTELA T, NORDSTROM D: Effectiveness of anakinra in rheumatic disease in patients naive to biological drugs or previously on TNF blocking drugs: an observational study. Clin Rheumatol .: 2006
    Organism: Division of Medicine, Helsinki University Central Hospital, Haartmanink 4, 00290, Helsinki, Finland, dannordstrom@husfi
    Abstract: The aim of this study was to evaluate the effectiveness of IL-1 inhibition in rheumatic disease using real-life, observational methods. We analyzed data from 47 patients collected from the national ROB-FIN for rheumatic disease. Commonly used, validated measures of efficacy and adverse effects were documented and analyzed. The series contains 47/1,135 patients (mean age 47+/-11 years, range 25-73, females 83%) on anakinra of whom 39 patients suffered from rheumatoid arthritis (RA), two presented with psoriatic arthritis, and four with juvenile RA. At 3 months (26/40), 46% reached American College of Rheumatology (ACR) 20 and 27% ACR 50. In patients naive to biological drugs, the response rate at 3 months was 60% for ACR 20 and 20% for ACR 50. At follow-up of the total series, ACR responses at 6 and 12 months were 69/56% for ACR 20 and 23/22% for ACR 50. These data give room for IL-1 suppression when treating patient with rheumatic disease. Careful selection of patients, together with combining anakinra with disease-modifying antirheumatic drugs, perhaps adds effectiveness. For treating clinicians in Finland, these results are encouraging, as reimbursed treatment alternatives for patients refractory to all other therapies are still few

14. MARTINI G, ZULIAN F: Juvenile idiopathic arthritis: current and future treatment options. Expert Opin Pharmacother 7:4 387-399, 2006
    Organism: Department of Pediatric Rheumatology, University of Padua, ItalyFAU - Martini, Giorgia
    Abstract: Juvenile idiopathic arthritis is the most common rheumatic disease in children. The management of juvenile idiopathic arthritis has improved in recent decades, and morbidity due to the disease is significantly decreased. In particular, the use of more effective drugs and their combination has changed the course of the disease in many patients. The increasing knowledge of inflammation mechanisms has lead to the development of new agents that target specific cytokines interfering with the inflammatory cascade. In particular, anti-TNF agents seem effective: etanercept is the only one licensed for juvenile idiopathic arthritis, and Phase III trials on two other anti-TNF agents, infliximab and adalimumab, are ongoing. This review discusses the current practice in the medical management of juvenile idiopathic arthritis, and potential new agents are discussed

15. PAMUK ON, PAMUK GE, USTA U, CAKIR N: Hemophagocytic syndrome in one patient with adult-onset Still's disease / Presentation with febrile neutropenia. Clin Rheumatol .: 2006
    Organism: Department of Rheumatology, Trakya University Medical Faculty, Edirne, Turkey, omernpamuk@yahoocom
    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

16. PHAROAH DS, VARSANI H, TATHAM RW, NEWTON KR, DE JAGER W, PRAKKEN BJ, KLEIN N, WEDDERBURN LR: Expression of the inflammatory chemokines CCL5, CCL3 and CXCL10 in juvenile idiopathic arthritis, and demonstration of CCL5 production by an atypical subset of CD8+ T cells. Arthritis Res Ther 8:2 R50, 2006
    Organism: Rheumatology Unit, Institute of Child Health, UCL, London, UK lwedderburn@ichuclacuk
    Abstract: ABSTRACT : This study focuses upon three chemokines, namely CCL5, CXCL10 and CCL3, which are potential novel therapeutic targets in arthritis. The aim of the study was to analyse the expression and production of these three chemokines within the joints of children with juvenile idiopathic arthritis (JIA) of the oligoarticular and polyarticular subtypes. All three of these chemokines are highly expressed at the level of mRNA, with the most significant increase in mRNA levels being demonstrated for CCL5 when compared with matched peripheral blood samples and controls. We show that high levels of all three chemokines are present in synovial fluid of children with JIA. We investigate the major source of CCL5 from inflammatory synovial cells, which we show to be CD8+ T cells. This CD8+ synovial T cell population has an unexpected phenotype that has not been described previously, being CCR7- yet predominantly CD28+ and CD45RA-. These cells contain high levels of stored intracellular CCL5, and rapid release of CCL5 takes place on T cell stimulation, without requiring new protein synthesis. In addition, we demonstrate that CCL5 is present in synovial biopsies from these patients, in particular on the endothelium of small and medium sized vessels. We believe this to be the first in depth analysis of these mediators of inflammation in JIA

17. ROBERTSON L: When should young people with chronic rheumatic disease move from paediatric to adult-centred care? Best Practice and Research in Clinical Rheumatology (United Kingdom ), 20/2 (387-397) 20:2 387-397, 2006
    Abstract: Many young people with childhood-onset diseases, including rheumatic diseases, continue to require medical care into adult life. There are many differences between paediatric and adult health care which can make this change a dramatic and difficult one for young people and their families. Transitional care services aim to equip young people with the appropriate knowledge and skills to cope with this change. This chapter will describe the differences between transition and transfer, and the different perspectives of those involved in the transition process, and will discuss the determinants of a successful transfer. Transition models currently used in practice will also be described, as will the evolving evidence base that is contributing to the further development of transitional care services. (c) 2005 Elsevier Ltd. All rights reserved

18. SAWHNEY S, MAGALHAES CS: Paediatric rheumatology--a global perspective. Best Pract Res Clin Rheumatol 20:2 201-221, 2006
    Organism: Department of Paediatric Rheumatology, Centre for Child Health, Sir Ganga Ram Hospital, New Delhi 110060, India sujatasawney@vsnlnetFAU - Sawhney, Sujata
    Abstract: This chapter aims to give a global perspective to paediatric rheumatology. The main points covered are the incidence, recognition of paediatric autoimmune diseases, and ethnic/geographic distribution. The most prevalent disease is juvenile idiopathic arthritis; robust data are still required for childhood-onset systemic lupus erythematosus, dermatomyositis, and scleroderma. Mimicking or overlapping infections are a major challenge in developing countries, and immunization policies in our patients in these areas need specific attention. The delivery of paediatric rheumatology care is also overviewed. Discrepancies in health-care resources and priorities are found in developing countries. Although most anti-rheumatic treatments are available worldwide, they are prohibitively expensive in many countries. For more traditional anti-rheumatic drugs there is still an ongoing need for good core outcome data across the world to ensure valid comparisons. Parent/patient education has been implemented worldwide in paediatric rheumatology through the power of the Internet. Physician and undergraduate training goals must be met to facilitate competent musculoskeletal assessment, a proper understanding of age-dependent variations, diagnosis, referral to specialists, and improved standards of care

19. SAXENA N, MISRA R, AGGARWAL A: Is the enthesitis-related arthritis subtype of juvenile idiopathic arthritis a form of chronic reactive arthritis? Rheumatology (Oxford) .: 2006
    Organism: Department of Immunology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India
    Abstract: Objective. Enteric organisms are known to trigger reactive arthritis. The enthesitis-related arthritis (ERA) form of juvenile idiopathic arthritis (JIA) clinically resembles reactive arthritis. Therefore, we looked for a role of enteric bacteria in ERA. Methods. Synovial fluid (SF) was obtained from 26 patients with ERA and 10 patients with rheumatoid arthritis (RA). Blood specimens were also obtained from patients with ERA and from 10 normal individuals. Lymphocyte proliferation assays were done on whole blood and SF mononuclear cells using as antigens crude lysates of the enteric bacteria Salmonella typhimurium, Yersinia enterocolitica, Shigella flexneri and Campylobacter jejuni. Crude lysate of Escherichia coli was used as a control antigen. HLA-B27 typing was done using the polymerase chain reaction. Homing of gut-specific T cells (CD103(+)) to the synovial compartment was studied using tri-colour flow cytometry. The antigen-specific cytokine profile was determined by flow cytometry. Results. Antigen-specific lymphoproliferative responses were observed in 14 of 26 patients. Among these patients, 12 showed a response in SF (four each to S. typhimurium and C. jejuni, and in two each to S. flexneri and Y. enterocolitica), and two patients in blood (S. typhimurium in both). None of the healthy controls showed a response in the blood. Lymphoproliferative responses in SF were more frequent in patients with JIA (12/26) than in controls with RA (1/10, P<0.05). Patients with an antigen-specific response had a higher ratio of SF/blood CD103(+) T cells compared with those with no antigen-specific response (P<0.01). Antigen-specific as well as mitogen-stimulated cytokine production showed a Th1 bias. Conclusion. Enteric bacteria may have a role in exacerbation of disease in patients with ERA. The immune response in patients with ERA is Th1-dominant

20. SCHEINBERG M, HAMERSCHLAK N, KUTNER JM, RIBEIRO AA, FERREIRA E, GOLDENBERG J, KISS MH, CHAHADE WH: Rituximab in refractory autoimmune diseases: Brazilian experience with 29 patients (2002-2004). Clin Exp Rheumatol 24:1 65-69, 2006
    Organism: Hospital Israelita Albert Einstein, Sao Paulo, Brazil morton@ositecombrFAU - Scheinberg, M
    Abstract: OBJECTIVE: Rituximab, a monoclonal antibody against B-lymphocytes that express CD 20, is already available for the treatment of non-Hodgkin's lymphoma. Due to the increased relevance of B-cell regulation in the pathogenesis of autoimmune diseases, rituximab is being used in the treatment of patients whose condition is refractory to conventional therapy. METHODS: We retrospectively evaluated the short-term efficacy and tolerance of rituximab in patients with various autoimmune diseases who were treated at the Hospital Israelita Albert Einstein in the city of Sao Paulo. RESULTS: During the period 2002-2004, 29 patients with various autoimmune diseases were treated with rituximab 375 mg/m2 for 4 consecutive weeks, or two doses of 1 g 2 weeks apart. We observed remarkable short-term results in all cases, except for one patient with thrombocytopenic purpura. Of note, we describe the results in two patients with diseases not previously treated with rituximab (hypergammaglobulinemic purpura of Waldenstrom and eosinophilic fasciitis with hypergammaglobulinemia). Treatment was well tolerated, with no unexpected adverse events. We also observed a marked reduction in steroid dosage. CONCLUSION: Rituximab seems to be safe and effective in the treatment of patients with a variety of autoimmune diseases that are refractory to other modalities of treatment

21. SCHEUNEMANN I, DANNECKER GE, ROTH J: Phalangeal bone ultrasound is of limited value in patients with juvenile idiopathic arthritis. Rheumatology (Oxford) .: 2006
    Organism: University Children's Hospital, 72076 Tubingen, Germany
    Abstract: Objective. In children with juvenile idiopathic arthritis (JIA), alterations of the skeletal system have been described. The aim of this cross-sectional study was to evaluate a phalangeal bone ultrasound device in the assessment of the skeletal status in children with active JIA. Methods. In 49 children with oligoarticular, polyarticular or systemic JIA, the speed of an ultrasound signal (Ad-SOS) through the phalanges of the dominant hand was measured using the Igea 1200. Results. Children in all subgroups were significantly smaller than those in the reference population, but there were no significant deficits in Ad-SOS. The finger width was reduced only in patients with polyarticular JIA. The Ad-SOS correlated highly with height, but no correlation between the finger width and Ad-SOS, and no correlation between the standard deviation scores of body height and Ad-SOS were seen. Conclusions. Phalangeal ultrasound is strongly dependent on body and therefore bone size, but other parameters of bone and soft tissues influence the measurements as well. It is not possible to differentiate as to which extent the various components of bone and soft tissue influence the measurement results. Ultrasound might therefore be of limited value in the assessment or screening of the skeletal system in children with JIA

22. SCHMELING H, WAGNER U, PETERSON A, HORNEFF G: Tumor necrosis factor alpha promoter polymorphisms in patients with juvenile idiopathic arthritis. Clin Exp Rheumatol 24:1 103-108, 2006
    Organism: Department of Pediatrics, Martin-Luther University Halle-Wittenberg, GermanyFAU - Schmeling, H
    Abstract: OBJECTIVE: To investigate the potential association of tumor necrosis factor-alpha (TNF) promoter alleles within subtypes of juvenile idiopathic arthritis (JIA) compared to healthy controls in a Caucasian population. METHODS: TNF-alpha promoter polymorphisms at positions -163, -238, -244, -308, -376 were determined in 228 patients with JIA and 196 healthy individuals. Genomic DNA was isolated and a PCR fragment of about 500 base pairs of the TNF gene promoter were amplified by PCR. Detection of polymorphisms was achieved by a single sequencing procedure. RESULTS: The TNF -238A allele was more frequent in the psoriatic arthritis JIA subgroup compared to healthy controls as well as to non-psoriatic JIA patients (p < 0.001, chi-square-test) and was associated with the more frequent occurrence of joint erosion (p < 0.05, chi-square-test). The frequency of the TNF -308A allele was significantly lower in patients with rheumatoid factor negative polyarthritis JIA patients compared to healthy controls, respectively (p < 0.05, chi-square-test). Joint erosions were detectable more often in rheumatoid factor negative polyarthritis JIA patients with the G/A genotype (80%) than in those with the G/G genotype (45%) (p = 0.20). The rare alleles at position -376 or at positions -163 and -244 were found very infrequently. CONCLUSION: TNF promoter polymorphisms may play a role in the pathogenesis of JIA. The TNF-238A allele seems to be associated with juvenile psoriatic arthritis. The TNF-308A allele is less frequently found in rheumatoid factor negative but not in rheumatoid factor positive polyarthritis and may therefore be associated with a more severe disease, while the more common TNF-308G allele may be protective

23. SMOLEN JS, VAN DER HEIJDE DM, ST CLAIR EW, EMERY P, BATHON JM, KEYSTONE E, MAINI RN, KALDEN JR, SCHIFF M, BAKER D, HAN C, HAN J, BALA M: Predictors of joint damage in patients with early rheumatoid arthritis treated with high-dose methotrexate with or without concomitant infliximab: results from the ASPIRE trial. Arthritis Rheum 54:3 702-710, 2006
    Organism: Medical University of Vienna and Lainz Hospital, Vienna, AustriaFAU - Smolen, Josef S
    Abstract: OBJECTIVE: To identify disease characteristics leading to progression of joint damage in patients with early rheumatoid arthritis (RA) treated with methotrexate (MTX) versus those treated with infliximab plus MTX. METHODS: Patients who had not previously been treated with MTX with active RA were randomly assigned to receive escalating doses of MTX up to 20 mg/week plus placebo or infliximab at weeks 0, 2, and 6, and every 8 weeks thereafter through week 46. Radiographic joint damage was assessed using the modified Sharp/van der Heijde score (SHS). The relationship between disease activity measures at baseline and week 14, as well as those averaged over time, were examined in relation to the change in SHS from baseline through week 54. RESULTS: C-reactive protein (CRP) levels, erythrocyte sedimentation rate (ESR), and swollen joint count were associated with greater joint damage progression in the MTX-only group, while none of these parameters was associated with progression in the infliximab plus MTX group. Mean changes in SHS among patients in the highest CRP (> or = 3 mg/dl) and ESR (> or = 52 mm/hour) tertiles in the MTX-only group were 5.62 and 5.89, respectively, compared with 0.73 and 1.12 in the infliximab plus MTX group (P < 0.001). Patients with greater joint damage at baseline (SHS > or = 10.5) showed less progression with infliximab plus MTX compared with MTX alone (-0.39 versus 4.11; P < 0.001). Patients receiving MTX alone who had persistently active disease at week 14 showed greater radiographic progression of joint damage than those taking MTX plus infliximab. CONCLUSION: High CRP level, high ESR, or persistent disease activity was associated with greater radiographic progression in the group taking MTX alone, while little radiographic progression was seen in patients receiving both MTX and infliximab, regardless of the abnormal levels of these traditional predictors

24. SOUZA L, MACHADO SH, BREDEMEIER M, BRENOL JC, XAVIER RM: Effect of inflammatory activity and glucorticoid use on nutritional variables in patients with juvenile idiopathic arthritis. J Rheumatol 33:3 601-608, 2006
    Organism: Division of Rheumatology, Hospital de Clinicas de Porto Alegre, Faculdade de Medicina, Universidade Federal do Rio Grande do Sul, RS, BrazilFAU - Souza, Leticia
    Abstract: OBJECTIVE: To assess nutritional status in patients with juvenile idiopathic arthritis (JIA) and the influence of inflammatory activity and glucocorticoid use. METHODS: One hundred sixteen patients were evaluated. Disease subtype and disease activity were defined by the attending physician, and the cumulative glucocorticoid dose was recorded from chart review. Percentiles of body mass index (BMI) and triceps skinfold (TSF) and the Z score for height were determined: low weight and low adiposity were diagnosed when BMI and TSF were below the 5th percentile. Short stature was defined by a Z score of height for age < -2. Serum concentration of insulin-like growth factor-I (IGF-I) was measured by radioimmunoassay. RESULTS: The prevalences of low weight, low adiposity, and short stature were 16.4%, 20.7%, and 10.4%, respectively. Low IGF-I serum level was found in 14 patients (12.1%). The factors negatively associated with the Z score of height in multivariable regression analysis were disease duration (partial correlation coefficient -0.370, 95% confidence interval: -0.527 to -0.188; p < 0.001), erythrocyte sedimentation rate (ESR) (-0.357, -0.516 to -0.174; p < 0.001), and polyarticular or systemic disease subtype (-0.290, -0.459 to -0.100; p = 0.003), while there was no significant correlation with the cumulative dose of glucocorticoids (0.086, -0.111 to 0.277; p = 0.391). None of these variables was significantly correlated with the percentiles of BMI and TSF, albeit confidence intervals for these correlation coefficients were relatively large. Patients with a systemic or polyarticular disease subtype tended to present lower percentiles of BMI (p = 0.051). CONCLUSION: Nutritional status is frequently compromised in patients with JIA. Duration and disease subtype and the ESR are factors independently associated with short stature. The cumulative dose of glucocorticoids was not independently associated with short stature or with other nutritional variables, although a relevant negative effect of glucocorticoid dose on BMI and TSF cannot be entirely excluded

25. STINSON JN, PETROZ GC, TAIT G, FELDMAN BM, STREINER D, MCGRATH PJ, STEVENS BJ: e-Ouch: usability testing of an electronic chronic pain diary for adolescents with arthritis. Clin J Pain 22:3 295-305, 2006
    Organism: Faculty of Nursing, University of Toronto, Toronto, Ontario, Canada jenniferstinson@sickkidscaFAU - Stinson, Jennifer N
    Abstract: OBJECTIVES: The aim of this study was to evaluate the usability of the e-Ouch electronic chronic pain diary in adolescents with juvenile idiopathic arthritis. METHODS: A qualitative usability testing approach with semistructured, audiotaped interviews with two iterative cycles was used. A purposive sample of 10 adolescents per cycle was drawn from a rheumatology clinic in a university-affiliated pediatric tertiary care center. Participants were provided with a brief demonstration of the diary and then asked to use the diary "thinking aloud" to record the pain they experienced: (1) when they woke up that morning, (2) during that afternoon, and (3) from the previous evening. Adolescents were then asked a series of open-ended questions addressing ease of use of the diary. Qualitative thematic analysis was used to generate categories and emerging themes from interview data. RESULTS: All of the adolescents stated the e-Ouch diary was very easy to learn, use, and understand and was satisfying to complete. Participants took less than 9 minutes to complete all three of the diary entries with minimal errors. The usability evaluation revealed aspects of the interface that were suboptimal (eg, VAS slider) and impeded the performance of certain tasks. Adolescents generated ideas on how the diary interface could be improved. CONCLUSIONS: A multifaceted usability approach provided important insight regarding the use of technology by adolescents with arthritis and, more specifically, for understanding how adolescents can more effectively use an electronic chronic pain diary

26. SUGIURA T, MAENO N, KAWAGUCHI Y, TAKEI S, IMANAKA H, KAWANO Y, TERAJIMA-ICHIDA H, HARA M, KAMATANI N: A promoter haplotype of the interleukin-18 gene is associated with juvenile idiopathic arthritis in the Japanese population. Arthritis Res Ther 8:3 R60, 2006
    Organism: Institute of Rheumatology, Tokyo Women's Medical University School of Medicine, 10-22 Kawada-cho, Shinjuku-ku, Tokyo, Japan y-kawa@iortwmuacjp
    Abstract: ABSTRACT : Recently, we reported that genetic polymorphisms within the human IL18 gene were associated with disease susceptibility to adult-onset Still's disease (AOSD), which is characterized by extraordinarily high serum levels of IL-18. Because high serum IL-18 induction has also been observed in the systemic type of juvenile idiopathic arthritis (JIA), we investigated whether similar genetic skewing is present in this disease. Three haplotypes, S01, S02, and S03, composed of 13 genetic polymorphisms covering two distinct promoter regions, were determined for 33 JIA patients, including 17 with systemic JIA, 10 with polyarthritis, and 6 with oligoarthritis. Haplotypes were also analyzed for 28 AOSD patients, 164 rheumatoid arthritis (RA) patients, 102 patients with collagen diseases, and 173 healthy control subjects. The frequency of individuals carrying a diplotype configuration (a combination of two haplotypes) of S01/S01 was significantly higher in the JIA patients, including all subgroups, than in the healthy controls (P = 0.0045, Fischer exact probability test; odds ratio (OR) = 3.55, 95% confidence interval (CI) = 1.55-8.14). In patients with systemic JIA, its frequency did not differ statistically from that of normal controls. Nevertheless, it is possible that haplotype S01 is associated with the phenotype of high IL-18 production in systemic JIA because the patients carrying S01/S01 showed significantly higher serum IL-18 levels compared with patients with other diplotype configurations (P = 0.017, Mann-Whitney U test). We confirmed that the frequency of the diplotype configuration of S01/S01 was significantly higher in AOSD patients than in healthy control subjects (P = 0.011, OR = 3.45, 95% CI = 1.42-8.36). Furthermore, the RA patients were also more predisposed to have S01/S01 (P = 0.018, OR = 2.00, 95% CI = 1.14-3.50) than the healthy control subjects, whereas the patients with collagen diseases did not. In summary, the diplotype configuration of S01/S01 was associated with susceptibility to JIA as well as AOSD and RA, and linked to significantly higher IL-18 production in systemic JIA. Possession of the diplotype configuration of S01/S01 would be one of the genetic risk factors for susceptibility to arthritis in the Japanese population

27. SUPPIAH V, ROONEY M, VANDENBROECK K: Polymorphisms in the interleukin-4 and IL-4 receptor genes modify risk for chronic inflammatory arthropathies in women. Exp Mol Pathol .: 1919
    Organism: Applied Genomics Research Group, McClay Research Centre, The Queen's University of Belfast, Belfast BT9 7BL, Northern Ireland, UK
    Abstract: Rheumatoid and juvenile idiopathic arthritis (RA, JIA) are chronic inflammatory arthropathies with polygenic autoimmune background. We analysed the IL-4 +33 C/T and IL-4R Q551R single nucleotide polymorphisms (SNPs) in 294 RA, 72 JIA and 165 controls from Northern Ireland. Analysis of the individual phenotypes (RA or JIA) showed that both the IL-4 +33 TT (P = 0.02; OR: 0.25, 95% CI: 0.07-0.87) and the IL-4R Q551R CC genotypes (P = 0.001; OR: 0.19, 95% CI: 0.06-0.56) were exclusively decreased in female RA patients compared to female controls. Similar non-significant trends were observed in female JIA patients (OR: 0.25, 95% CI: 0.03-2.11 and OR: 0.31, 95% CI: 0.07-1.47, respectively). Analysis of the common phenotype (inflammatory arthropathy; i.e. JIA and RA combined) corroborated the unique association of these polymorphisms with female inflammatory arthropathy (P = 0.013 and 0.002, respectively). This is the first demonstration of sex-specific association of the two foremost genes of the IL-4 signalling cascade with chronic inflammatory arthropathies

28. TANAKA H, TSUGAWA K, NAKAHATA T, SUZUKI K, ITO E: Leukocytapheresis for the treatment of refractory systemic-onset juvenile idiopathic arthritis. Clin Rheumatol .: 2006
    Organism: Department of Pediatrics, Hirosaki University School of Medicine, 5 Zaifu-cho, Hirosaki, 036-8562, Japan, hirotana@cchirosaki-uacjp
    Abstract: Although leukocytapheresis (LCAP) has been reported to be effective for the treatment of various autoimmune disorders, little information has been published yet on the efficacy and safety of LCAP for the treatment of systemic-onset juvenile idiopathic arthritis (SOJIA). A pilot trial of LCAP was therefore conducted on two children with refractory SOJIA using a granulocyte apheresis filter packed with cellulose acetate beads in an attempt to control the disease flares. Following three to eight sessions of LCAP, the joint symptoms gradually resolved without any increase in the dose of corticosteroids. The procedure was associated with a decrease in the serum interleukin-6. No severe adverse effects were observed except for mild nausea. However, efficacy of LCAP sustained in a short time since both patients subsequently developed flares after 3 months of the treatment

29. TAUBER T, TURETZ J, BARASH J, AVNI I, MORAD Y: Optic neuritis associated with etanercept therapy for juvenile arthritis. J AAPOS 10:1 26-29, 2006
    Organism: Pediatric Rheumatology Clinic, Assaf Harofeh Medical Center, Zrifin, IsraelFAU - Tauber, Tsivia
    Abstract: PURPOSE: We sought to describe cases of optic neuritis associated with etanercept therapy. METHODS: A retrospective chart review was undertaken on all patients that developed uveitis or optic neuritis associated with etanercept therapy between January 2003 and January 2005 in 2 medical centers: Assaf Harofeh Medical Center, and Kaplan Medical Center, Israel. RESULTS: Four patients (3 girls, 1 boy) treated with etanercept for juvenile idiopathic arthritis (JIA) are presented. The 3 girls had oligoarticular-onset JRA. The boy had HLA-B27-positive juvenile spondyloarthropathy and bilateral uveitis. After a mean follow-up of 10 months (range, 2.5-18 months) all 4 patients had reduced visual acuity due to optic neuritis, which was accompanied by vitreitis in 2 eyes. In 3 patients, the discontinuation of etanercept, together with steroid treatment, resulted in resolution of the inflammation. The fourth patient elected to continue etanercept treatment and experienced no further deterioration in visual acuity. CONCLUSION: Optic neuritis is a potentially sight-threatening complication of etanercept therapy. Patients with JRA who are candidates for therapy should be examined by an ophthalmologist before starting treatment and then regularly thereafter. Ophthalmologists and rheumatologists should be aware of this hazard and be cautious when using etanercept in this patient population

30. WALLACE CA: Current management of juvenile idiopathic arthritis. Best Pract Res Clin Rheumatol 20:2 279-300, 2006
    Organism: Division of Immunology, Rheumatology and Infectious Diseases, Children's Hospital and Regional Medical Center, University of Washington School of Medicine, 4800 Sandpoint Way NE MS-B-6583, Seattle, WA 98105, USA cwallace@uwashingtoneduFAU - Wallace, Carol A
    Abstract: The goal of juvenile idiopathic arthritis (JIA) treatment is to achieve remission of disease. The absence of a full understanding of the disease pathogenesis for JIA hinders the development of truly effective treatment approaches. Further, the lack of clear knowledge regarding the mechanisms of action of rheumatologic medications and the existence of few randomized controlled trials leaves clinicians with very little evidence upon which to base decisions regarding the best timing, dosages or combinations of medications to be used for fully effective treatment of JIA. There is now a shift in treatment focus from that of chasing failure (gradual add-on approach to the use of medications) to one of early aggressive combination treatment. This chapter will discuss the current approaches to medical management of JIA and the medications currently available for use. JIA treatment is a vast, rich area in need of research

31. WOLPAW TM, BAER AN, GALL EP, MILLER ML, NOSS EH, O'NEIL KM: Winners of the 2005 American College of Rheumatology Annual Slide Competition. Arthritis Rheum 54:3 690-691, 2006