Bibliography May 2008

1. ABAD VC, SARINAS PSet GUILLEMINAULT C: Sleep and rheumatologic disorders, Sleep Med.Rev., Vol. 12(3), 211-228., 2008
   Organism:Clinical Monitoring Sleep Disorders Center, Camino Medical Group, Palo Alto Medical Foundation, USAFAU - Abad, Vivien C
   Abstract:Arthritis is the leading cause of chronic illness in the United States. Seventy-two percent of the adults aged 55 years and older with arthritis report sleep difficulties. This review discusses sleep disorders associated with rheumatoid arthritis, juvenile rheumatoid arthritis, Sjogren's syndrome, systemic lupus erythematosus, scleroderma, Behcet's disease, seronegative spondyloarthropathies, osteoarthritis, sarcoidosis, and fibromyalgia. We describe the inter-relationship between sleep complaints, disease activity, depression, sleep deprivation, and cytokines. An algorithm for evaluation and treatment of sleep disorders associated with rheumatologic diseases is proposed

2. ADACHI Y, YOSHIO-HOSHINO Net NISHIMOTO N: The blockade of IL-6 signaling in rational drug design, Curr.Pharm.Des., Vol. 14(12), 1217-1224., 2008
   Organism:Laboratory of Immune Regulation, Graduate School of Frontier Biosciences, Osaka University, Osaka, JapanFAU - Adachi, Yasuo
   Abstract:After three decades from the development of the hybridoma technology, a monoclonal antibody-based therapy targeting the inflammatory cytokine has been established as an ultimate treatment for chronic inflammatory diseases. Interleukine-6 (IL-6) is one of the inflammatory cytokines playing a pivotal role in these conditions, and strategies targeting IL-6 signal show promise in the treatment of chronic inflammatory diseases such as rheumatoid arthritis, juvenile idiopathic arthritis, and Crohn's disease. Although many groups have been exploring the approach to block the IL-6 signal, tocilizumab, a humanized monoclonal antibody of the IL-6 receptor, has been the most intensively studied agent for clinical use. Clinical trials regarding chronic inflammatory diseases described above have demonstrated efficacy of tocilizumab, however, this treatment has limitations in terms of economic costs and ease of administration, and further advances are necessary to expand the concept of IL-6-specific therapeutics. In this review, we discuss targeting IL-6 in a rational drug design and present the various strategies to achieve this

3. DING Cet JONES G: Anti-interleukin-6 receptor antibody treatment in inflammatory autoimmune diseases, Rev.Recent Clin.Trials., Vol. 1(3), 193-200., 2006
   Organism:Menzies Research Institute, Hobart, Tasmania, Australia changhaiding@utaseduauFAU - Ding, Changhai
   Abstract:Tocilizumab (namely MRA), a humanized anti-interleukin (IL)-6 receptor monoclonal antibody, is under development by Roche for the treatment of inflammatory autoimmune diseases such as rheumatoid arthritis (RA), systemic onset juvenile idiopathic arthritis (JIA), adult-onset Still's disease, Castleman's disease and Crohn's disease. Tocilizumab has a long plasma half-life, so it can be administered intravenously biweekly or monthly. Phase I and II clinical trials showed that tocilizumab (2, 4, 5, 8 or 10 mg/kg) reduced disease activity significantly in a dose-dependent manner. Tocilizumab not only improved signs and symptoms, but also normalized inflammatory markers such as C-reactive protein, erythrocyte sedimentation rate (ESR), fibrinogen and serum amyloid A, and reversed joint damage of RA. The efficacy of tocilizumab in the treatment of RA was at least as good as methotrexate. Tocilizumab was generally safe and well tolerated. Some adverse events such as significant rises in total cholesterol and triglyceride levels, liver function disorders, decreases in white blood cell counts, diarrhoea and infection were observed. In summary, preliminary clinical results suggest that tocilizumab is effective and generally well tolerated in the treatment of IL-6-related inflammatory autoimmune diseases. Like other anti-cytokine immunotherapies, caution and close monitoring for the adverse events, especially infection, are necessary in subsequent clinical trials

4. FUCHS BSet HADI S: Use of etanercept in the treatment of psoriasis and psoriatic arthritis, Rev.Recent Clin.Trials., Vol. 1(3), 259-263., 2006
   Organism:Mount Sinai School of Medicine, One Gustave L Levy Place, New York, NY 10029, USAFAU - Fuchs, Brian S
   Abstract:Psoriasis and psoriatic arthritis are debilitating inflammatory immunemediated diseases which are chronic in nature and often require lifelong attention. Traditional therapies used to combat these diseases lack sufficient long-term efficacy and are associated with a number of toxicities. Failing to adequately satisfy both patients and physicians, traditional therapies have proven insufficient and have left few options. Etanercept is a tumor necrosis factor (TNF) antagonist that reduces elevated TNF levels by competitively binding to both TNF-alpha and TNF-beta and inhibiting the proinflammatory cascade. Providing a valuable treatment option alone, etanercept can also be effectively administered in conjunction with traditional treatments. Etanercept is self administered by subcutaneous (SC) injection, making treatment less of a burden for patients by eliminating the need for frequent office visits and laboratory testing. Etanercept is approved in the US for the treatment of psoriasis, psoriatic arthritis, rheumatoid arthritis, juvenile rheumatoid arthritis, and ankylosing spondylitis

5. HASSAN J, VAN DER NJ, HELDERS PJ, PRAKKEN BJet TAKKEN T: Six-minute Walk Test in Children with Chronic Conditions, Br.J.Sports Med., Vol. ., 2008
   Organism:Wilhelmina Children's Hospital, University Medical Centre Utrecht, Netherlands
   Abstract:OBJECTIVES: The six-minute walk test (6MWT) is a frequently used indicator of functional exercise capacity. The goals of this study were to compare the six-minute walk performance of three paediatric patient groups with that of healthy peers, to assess differences between published reference values and to investigate which anthropometric characteristics best predict six-minute walk performance. METHODS: Forty-seven children with haemophilia (mean +/- SD age 12.5 +/- 2.9), forty-four with juvenile idiopathic arthritis (JIA) (mean +/- SD age 9.3 +/- 2.2) and twenty-two with spina bifida (SB) (mean +/- SD age 10.3 +/- 3.1) were included. Subjects performed a 6MWT and the distance walked (6MWD) was compared with published reference values. RESULTS: The haemophilia, JIA, and SB patients respectively achieved 90-92%, 72-75% and 60-62% of predicted walking distances. There were significant associations between 6MWD and age, height and weight in the haemophilia group and 6MWD and height in the JIA group. None of the anthropometric variables was significantly related to 6MWD in the SB group. All anthropometric variables were strongly correlated with walking distance-body weight product (6Mwork) in all groups. Height explained 24% (haemophilia) and 11% (JIA) of the variance in 6MWD and 84% (haemophilia), 78% (JIA) and 73% (SB) of the variance in 6Mwork. CONCLUSIONS: Walking distances of children with haemophilia, JIA and SB are significantly reduced compared to healthy references. Walking distance-body weight product seems to be a better outcome measure of the 6MWT compared to distance walked alone. Height is the best predictor of 6MWD and 6Mwork

6. HEINZ C, PLEYER U, RUOKONNEN Pet HEILIGENHAUS A: [Secondary glaucoma in childhood uveitis.], Ophthalmologe., Vol. 105(5), 438-444., 2008
   Organism:Augenabteilung am St Franziskus Hospital Munster, Hohenzollernring 74, 48145, Munster, Deutschland, carstenheinz@uveitis-zentrumdeFAU - Heinz, C
   Abstract:Ocular hypertension and secondary glaucoma are frequent and challenging complications in childhood uveitis. They are commonly found in patients with panuveitis or anterior uveitis and are often associated with juvenile idiopathic arthritis. Angle closure is rare, while secondary open angle glaucoma accounts for the majority of cases and often continues after the acute inflammation has healed. Monitoring should include tonometry, perimetry, and the objective assessment of the optic disc and nerve fibre layer. First-line therapy should consist of topical carbonic anhydrase inhibitors, followed by beta blockers, and then the alpha-2 agonists. Topical therapy must be monitored closely, as drug-related systemic side effects may preferentially occur in children. Because topical therapy in children is commonly ineffective, surgical interventions are often required. Reports on the use of trabeculectomy, goniosurgery, glaucoma drainage devices, and cyclodestructive procedures show higher failure rates than when used for primary open angle glaucoma in adults

7. HEINZ C, MINGELS A, GOEBEL C, FUCHSLUGER Tet HEILIGENHAUS A: Chronic Uveitis in Children with and without Juvenile Idiopathic Arthritis: Differences in Patient Characteristics and Clinical Course, J.Rheumatol., Vol. ., 2008
   Organism:From the Department of Ophthalmology, St Franziskus-Hospital Muenster, Muenster; and University Duisburg, Essen, Germany
   Abstract:OBJECTIVE: Anterior uveitis (AU) in childhood may be the first manifestation of juvenile idiopathic arthritis (JIA). We identified factors that may help to differentiate JIA-associated AU from the more common idiopathic AU (IAU) before the onset of arthritis. METHODS: Children with IAU and with JIA-associated AU were analyzed for their demographics, age at onset of uveitis, uveitis course and complications, ocular surgery, antiinflammatory medication, and best corrected visual acuity (BCVA). RESULTS: AU was associated with JIA in 88 cases, and was idiopathic in another 49. In the JIA group, 60% of patients were female compared to 47% in the IAU group (p = 0.154). Antinuclear antibody (ANA) was significantly more frequent in the JIA group (88% vs 33%; p < 0.001, OR 14.4, 95% CI 5.8-35.6). Insidious uveitis onset occurred more often in JIA than in IAU patients (67% vs 31%; p < 0.001, OR 4.6, 95% CI 2.2-9.8). Persistent uveitis was found in 82% of JIA patients, and in 57% of IAU patients (p = 0.003, OR 3.4, 95% CI 1.5-7.4). Median age of AU onset was 5 years in JIA and 9 years in IAU (p < 0.001). Uveitis complications at first presentation at our institutions were more frequent in JIA than in IAU patients (79% vs 61%; p = 0.027, OR 2.5, 95% CI 1.1-5.3). During followup, 69 surgical procedures (51% of patients, 1.31 per patient) were performed in the JIA group, and 18 in IAU patients (0.57 per patient) (p = 0.008). BCVA was better in the IAU patients at first presentation (p = 0.001). CONCLUSION: The IAU and JIA-associated AU in childhood differ in their clinical course. ANA positivity, presence of uveitis complications at first manifestation, insidious onset, duration over 3 months, BCVA of 20/50 or less, and an age of 3 years or younger might help to detect AU associated with JIA. JIA uveitis manifests earlier, has more complications, and more often requires systemic immunosuppression and surgical intervention

8. JANSE AJ, SINNEMA G, UITERWAAL CS, KIMPEN JLet GEMKE RJ: Quality of life in chronic illness: children, parents and paediatricians have different, but stable perceptions, Acta Paediatr., Vol. ., 2008
   Organism:Department of Pediatrics, Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht, The Netherlands
   Abstract:Aim: Quality of life assessments can be helpful to estimate the well-being of chronically ill children. The aim of this study was to investigate the differences in perception of health-related quality of life (HRQoL) among children, parents and paediatricians at the time of diagnosis and after initial treatment in four chronic diseases. Methods: HRQoL was assessed with the Health Utilities Index mark 3 (HUI3). The HUI3 consists of eight attributes (vision, hearing, speech, ambulation, dexterity, emotion, cognition and pain). Results: Nineteen paediatricians and 60 patients (aged 10-17 years) and their parents with newly diagnosed acute lymphoblastic leukaemia, juvenile idiopathic arthritis, asthma or with cystic fibrosis admitted for pneumonia participated in the study. Health and well-being perceptions were clearly different among paediatricians, parents and patients, both at diagnosis and after initial treatment. Perception differences were more prominent in the subjective attributes, emotion and pain. The agreement for these attributes was 23% and 5%, respectively. Paediatricians assessed the patients to have less pain than the patients and parents did. The reverse was true for the attribute emotion. At follow-up, the agreement was higher for the attributes ambulation and pain. Conclusion: At the onset of a chronic disease and after initial treatment, paediatricians, parents and children have different perceptions of the child's quality of life, particularly as to the subjective attributes pain and emotion. In view of these differences in perception among patients, their caregivers and paediatricians, this study suggests that whenever possible, multi-respondent assessment of HRQoL should be considered

9. KANAKOUDI-TSAKALIDOU F, TZIMOULI V, PRATSIDOU-GERTSI P, CHRONOPOULOU Eet TRACHANA M: The significance of persistent newly developed autoantibodies in JIA patients under long-term anti-TNF treatment, Cytokine., Vol. 42(3), 293-297., 2008
   Organism:First Department of Pediatrics, Aristotle University, Ippokration General Hospital, 49 Konstantinoupoleos str, 54642 Thessaloniki, GreeceFAU - Kanakoudi-Tsakalidou, Florence
   Abstract:Objective: To study the significance of persistent (12 months) new autoantibodies, in Juvenile Idiopathic Arthritis (JIA) patients treated with either Infliximab (INFL) or Etanercept (ET) for 2 years. Patients-methods: 26 children under INFL (n=12) or ET (n=14) were prospectively studied. A large panel of autoantibodies was tested using indirect immunofluorescence (ANA, anti-dsDNA, anti-ENA, SMA, LKM, AMA, PCA, anti-R1, ATA), ELISA (ANA, anti-ENA, anti-cardiolipin, ANCA), immunoblotting assay (anti-ENA: anti-Ro, anti-La, anti-Sm, anti-URNP, anti-Jo, anti-Scl70, anti-centromere, anti-ribosomal and anti-histone) and rate nephelometry (RF). Results: Apart from the positive patients for ANA (13/26) and RF (2/26) prior to anti-TNF treatment, 6/26 patients (23%) developed new autoantibodies (SMA, anti-R1, ATA) which persisted for 12-50 months. None developed antibodies to nuclear antigens. In only one case, ATA was associated with the development of Hashimoto's thyroiditis. Conclusions: These findings indicate that in JIA patients in contrast to adult RA patients, development of new autoantibodies to various nuclear antigens is rare. Other non relevant to rheumatic diseases autoantibodies, may appear and persist for >12 months, but very rarely they may be related to clinical entities, especially in the presence of a positive family history of autoimmunity

10. KARVA AR, BOARD TNet PORTER ML: Conversion of bilateral hip and knee ankylosis to total joint replacements, J.Bone Joint Surg.Br., Vol. 90(5), 668-673., 2008
    Organism:The Centre for Hip Surgery, Wrightington Hospital, Hall Lane, Appley Bridge, Wigan, WN6 9EP, UKFAU - Karva, A R
    Abstract:We present a 25-year-old patient with juvenile rheumatoid arthritis and ankylosis of both hips and both knees treated by staged bilateral hip and knee arthroplasty. She was followed up for 18 months. We discuss the pre-operative planning, surgical details and post-operative rehabilitation

11. KIM HJ, KAHN Bet FIGGIE MP: Total joint replacement in childhood arthritis, Curr.Rheumatol.Rep., Vol. 10(2), 135-141., 2008
    Organism:Hospital for Special Surgery, 535 East 70th Street, New York, NY 10021, USAFAU - Kim, Han Jo
    Abstract:Juvenile rheumatoid arthritis poses a distinct challenge to pediatric rheumatologists and orthopedic surgeons. Recent developments in the medical management of juvenile rheumatoid arthritis have decreased the need for surgical intervention in this subset of patients; however, those patients who need surgery are often the most challenging cases due to their relatively small bone size, the complex deformity caused by soft tissue contractures, and the tendency for multiple joint involvement. Nonetheless, technologic improvements in implant design and surgical techniques have led to successful outcomes in otherwise debilitating conditions. A careful and coordinated approach to the surgical management of juvenile rheumatoid arthritis can lead to improved function and significant pain relief for children with rheumatoid arthritis

12. LIPIEC E, GRALEK Met NIWALD A: [Condition of organ of vision in children and adolescence with juvenile idiopathic arthritis], Klin.Oczna., Vol. 109(10-12), 428-431., 2007
    Organism:Kliniki Okulistyki Dzieciecej Katedry Pediatrii Zabiegowej Uniwersytetu Medycznego w LodziFAU - Lipiec, Ewa
    Abstract:PURPOSE: Among numerous complications pertaining to the internal organs in the course of inflammatory systemic diseases of the connective tissue, including juvenile idiopathic arthritis (JIA), eye lesions are of considerable significance. The aim of the study was to determine changes in the eyes in JIA children and adolescents. MATERIAL AND METHODS: The study included 76 children with JIA. The age of patients during the first ophthalmologic examination ranged from 3 to 18 years. The children were treated in the Outpatients' Rheumatologic Department at the University Hospital No. 4 in Lodz and Department of Pediatric Ophthalmology at the Medical University of Lodz. A control group consisted of 60 healthy children. In this study the time of observation was 18 months during which the children and adolescents were subjected to complex ophthalmologic examinations in the intervals of 9 months. RESULTS: The presence of various ocular changes were significantly more frequently found in children with JIA. The difference appeared to be statistically significant between the group of children with JIA and the control group, in the range of such diseases as conjunctivitis and pigment changes in the retina. CONCLUSIONS: In JIA patients ophthalmologic lesions are more frequent than in healthy children, especially it concerns conjunctivitis (in 34% of children) and pigment changes in the retina (in 14% of children)

13. MACDERMOTT EJet LEHMAN TJ: The role of gene transcript signature in diagnosing systemic onset juvenile idiopathic arthritis, Curr.Rheumatol.Rep., Vol. 10(2), 133-134., 2008
    Organism:

14. MARHAUG G, SHAH V, SHROFF R, VARSANI H, WEDDERBURN LR, PILKINGTON CAet BROGAN PA: Age-dependent inhibition of ectopic calcification: a possible role for fetuin-A and osteopontin in patients with juvenile dermatomyositis with calcinosis, Rheumatology (Oxford)., Vol. ., 2008
    Organism:Department of Paediatrics, Trondheim University Hospital, Department of Laboratory Medicine, Children's and Women's Health, The Norwegian University of Science and Technology, Trondheim, Norway, Department of Rheumatology, Great Ormond Street Hospital for Children, Department of Infectious Disease and Microbiology, Department of Nephrourology, Department of Rheumatology and Rheumatology Unit, UCL Institute of Child Health, London, UK
    Abstract:Objectives. To assess if age and/or age-dependent variations in the levels of two major calcification regulatory proteins, fetuin-A and osteopontin, could be associated with an increased risk of calcinosis in children with juvenile dermatomyositis (JDM). Methods. The frequency of calcinosis was derived from a national UK database of 212 cases of JDM. Serum fetuin-A and plasma osteopontin levels were determined using ELISA in 15 JDM patients with calcinosis and 15 JDM patients without calcinosis. Healthy controls were 19 age-matched children, 24 adolescents and 13 adults. Sixteen patients with juvenile idiopathic arthritis (JIA) were additional paediatric disease controls. Results. Of the 212 JDM cases 10% had calcinosis. Calcinosis patients had younger age of disease onset than those without calcinosis (mean age of 5.3 yrs vs 7.1 yrs, respectively, P = 0.016). No significant difference in fetuin-A or osteopontin could be detected between the two JDM groups. Fetuin-A levels in all groups of children and the adolescent group were much lower than described previously in adults, and there was a significant positive correlation between age and fetuin-A level, and also between osteopontin levels in plasma and serum fetuin-A. Conclusions. Children who develop JDM at an younger age may have increased risk of developing calcinosis. Physiologically low levels of fetuin-A in young children combined with an additional negative acute-phase effect on fetuin-A due to chronic inflammation could explain in part the propensity to develop ectopic calcification observed in JDM patients, and why calcinosis is less frequent in adults with dermatomyositis

15. MCKEON A, LENNON VA, LOTZE T, TENENBAUM S, NESS JM, RENSEL M, KUNTZ NL, FRYER JP, HOMBURGER H, HUNTER J, WEINSHENKER BG, KRECKE K, LUCCHINETTI CFet PITTOCK SJ: CNS aquaporin-4 autoimmunity in children, Neurology., Vol. ., 2008
    Organism:From the Departments of Neurology (AM, VAL, NLK, BGW, CFL, SJP), Laboratory Medicine and Pathology (VAL, JPF, HH, SJP), Immunology (VAL), and Radiology (KK), Mayo Clinic College of Medicine, Rochester, MN; Divisions of Child Neurology (TL), and Radiology (JH), Texas Children's Hospital, Baylor College of Medicine, Houston; Department of Pediatric Neurology, National Pediatric Hospital Dr J P Garrahan (ST), Buenos Aires, Argentina; Department of Pediatrics, University of Alabama at Birmingham and Children's Hospital (JMN); and Division of Child Neurology, The Cleveland Clinic Foundation (MR), OH
    Abstract:BACKGROUND: In adult patients, autoantibodies targeting the water channel aquaporin-4 (AQP4) are a biomarker for a spectrum of CNS inflammatory demyelinating disorders with predilection for optic nerves and spinal cord (neuromyelitis optica [NMO]). Here we describe the neurologic, serologic, and radiographic findings associated with CNS AQP4 autoimmunity in childhood. METHODS: A total of 88 consecutive seropositive children were identified through service evaluation for NMO-IgG. Sera of 75 were tested for coexisting autoantibodies. Clinical information was available for 58. RESULTS: Forty-two patients (73%) were non-Caucasian, and 20 (34%) had African ethnicity. Median age at symptom onset was 12 years (range 4-18). Fifty-seven (98%) had attacks of either optic neuritis (n = 48; 83%) or transverse myelitis (n = 45; 78%), or both. Twenty-six (45%) had episodic cerebral symptoms (encephalopathy, ophthalmoparesis, ataxia, seizures, intractable vomiting, or hiccups). Thirty-eight (68%) had brain MRI abnormalities, predominantly involving periventricular areas (in descending order of frequency): the medulla, supratentorial and infratentorial white matter, midbrain, cerebellum, thalamus, and hypothalamus. Additional autoantibodies were detected in 57 of 75 patients (76%), and 16 of 38 (42%) had a coexisting autoimmune disorder recorded (systemic lupus erythematosus, Sjogren syndrome, juvenile rheumatoid arthritis, Graves disease). Attacks were recurrent in 54 patients (93%; median follow-up, 12 months). Forty-three of 48 patients (90%) had residual disability: 26 (54%) visual impairment and 21 (44%) motor deficits (median Expanded Disability Status Scale 4.0 at 12 months). CONCLUSIONS: Aquaporin-4 autoimmunity is a distinctive recurrent and widespread inflammatory CNS disease in children

16. PARIKH JG, TAWANSY KAet RAO NA: Immunohistochemical Study of Chronic Nongranulomatous Anterior Uveitis in Juvenile Idiopathic Arthritis, Ophthalmology., Vol. %20;., 2008
    Organism:A Ray Irvine Ocular Pathology Laboratory, the Doheny Eye Institute, Department of Ophthalmology, Keck School of Medicine of the University of Southern California, Los Angeles, California
    Abstract:PURPOSE: To provide a detailed immunohistochemical analysis of juvenile idiopathic arthritis (JIA)-associated anterior uveitis. DESIGN: Interventional case report. PARTICIPANT: One patient. INTERVENTION: A 12-year-old patient had recurrent pauciarticular JIA and smoldering anterior uveitis in the right eye. Despite treatment with local and systemic corticosteroids and an anti-tumor necrosis factor agent, the right eye became hypotonous and painful and eventually was enucleated. The clinical history and histopathologic and immunohistochemical analyses of the enucleated globe were reviewed. MAIN OUTCOME MEASURES: Histopathologic and immunohistochemical features of JIA-associated anterior uveitis. RESULTS: The iris and ciliary body showed nongranulomatous chronic inflammation predominantly made up of plasma cells, Russell bodies, and plasmacytoid lymphocytes. The ciliary processes and pars plana ciliaris showed focal aggregates of CD20-positive cells with several CD3- and CD8-positive cells and occasional CD4- and CD68-positive cells. Pancytokeratin stain showed ciliary epithelial proliferation admixed with lymphocytes. The iris revealed kappa-positive cells within the stroma and lambda-positive cells on the surface. The iris infiltrate primarily was made up of immunoglobulin (Ig) G-positive cells with occasional IgA- and IgM-positive cells. The anterior chamber exudate was mainly positive for IgG and IgA. CONCLUSIONS: The immunohistochemical findings suggest that JIA-associated nongranulomatous iridocyclitis is a primarily B-cell-infiltrative process

17. PETROPOULOS IK, VAUDAUX JDet GUEX-CROSIER Y: Anti-TNF-alpha Therapy in Patients with Chronic Non-Infectious Uveitis: The Experience of Jules Gonin Eye Hospital1, Klin.Monatsbl.Augenheilkd., Vol. 225(5), 457-461., 2008
    Organism:Jules Gonin Eye Hospital, University of Lausanne, Lausanne, Switzerland (Chairman: Prof L Zografos)FAU - Petropoulos, I K
    Abstract:BACKGROUND: The purpose of this study is to describe the experience of Jules Gonin Eye Hospital on the long-term outcome of anti-TNF-alpha therapy in chronic non-infectious uveitis. PATIENTS AND METHODS: We identified and followed those patients with chronic non-infectious uveitis who received systemic anti-TNF-alpha therapy. Anti-TNF-alpha therapy was administered when no response had been obtained with classical immunosuppressive therapies or in the presence of severe rheumatoid disease. RESULTS: Fifteen patients (28 eyes), 7 male and 8 female (mean age, 43 years; range: 7 to 70 years) were identified. Diagnoses included HLA-B27-associated anterior uveitis (n = 4), sarcoidosis (n = 2), juvenile idiopathic arthritis (n = 2), idiopathic retinal vasculitis with uveitis (n = 2), pars planitis (n = 2), Adamantiades-Behcet disease (n = 1), birdshot retinochoroidopathy (n = 1), and Crohn's disease (n = 1). Mean duration of ocular disease was 8 years (range: 1 to 29 years). Treatment with infliximab (n = 11), etanercept (n = 2), or adalimumab (n = 2) was initiated. One patient with etanercept was switched to infliximab due to lack of clinical response. Clinical and angiographic regression of uveitis was observed within the first two months of therapy in all patients, and was maintained throughout the entire follow-up period (mean 18 months; range: 3 - 72 months). Recurrence was observed in 3 patients, and resolved after adjustment of therapy. Adverse events were recorded in only one patient (arterial hypotension). CONCLUSIONS: In this series of patients with chronic non-infectious uveitis, anti-TNF-alpha therapy was effective and safe. Further clinical studies are needed to determine an adequate duration of therapy

18. PRAHALAD S, MARTINS TB, TEBO AE, WHITING A, CLIFFORD B, ZEFT AS, MCNALLY B, BOHNSACK JFet HILL HR: Elevated serum levels of soluble CD154 in children with juvenile idiopathic arthritis, Pediatr.Rheumatol.Online.J., Vol. 6(1), 8, 2008
    Organism:ABSTRACT: OBJECTIVE: Cytokines play important roles in mediating inflammation in autoimmunity. Several cytokines are elevated in serum and synovial fluid samples from children with Juvenile Idiopathic Arthritis (JIA). Soluble CD154 (sCD154) is elevated in other autoimmune disorders, but has not been characterized in JIA. Our objectives were to determine if sCD154 is elevated in JIA, and to examine correlations between sCD154 and other inflammatory cytokines. METHODS: Serum from 77 children with JIA and 81 pediatric controls was analyzed for interleukin (IL)1beta, IL2, IL4, IL5, IL6, IL8, IL10, IL12, IL13, sCD154, interferon-gamma (IFNgamma), soluble IL2 receptor (sIL2R), and tumor necrosis factor-alpha (TNFalpha), using the Luminex Multi-Analyte Profiling system. Differences in levels of cytokines between cases and controls were analyzed. Logistic regression was also performed. RESULTS: sCD154 was significantly elevated in cases compared to controls (p <0.0001). IL1beta, IL5, IL6, IL8, IL13, IFNgamma, sIL2R, and TNFalpha were also significantly elevated in JIA. Levels of sCD154 were highly correlated with IL1beta, IL6, IL8, and TNFalpha (p <0.0001). Logistic regression analysis suggested that IL6 (odds ratio (OR): 1.4, p <0.0001), sCD154 (OR: 1.1, p <0.0001), and TNFalpha (OR: 1.1, p <0.005) were positively associated with JIA, while IL10 (OR: 0.5, p <0.002) was protective. sCD154 was elevated in all JIA subtypes, with highest levels among more severe subtypes. IL1beta, IL6, IL8, sIL2R and TNFalpha were also elevated in several JIA subtypes. CONCLUSIONS: Serum levels of sCD154, IL1beta, IL6, IL8, sIL2R and TNFalpha are elevated in most JIA subtypes, suggesting a major role for sCD154, and these cytokines and cytokine receptors in the pathogenesis of JIA

19. RUPERTO N, MEIORIN S, IUSAN SM, RAVELLI A, PISTORIO Aet MARTINI A: Consensus procedures and their role in pediatric rheumatology, Curr.Rheumatol.Rep., Vol. 10(2), 142-146., 2008
    Organism:IRCCS G Gaslini, Pediatria II-PRINTO, University of Genoa, Largo Gaslini, 5, 16147 Genova, Italy nicolaruperto@ospedale-gaslinigeitFAU - Ruperto, Nicolino
    Abstract:The Delphi Technique and Nominal Group Technique are two well-recognized consensus-formation methodologies specifically designed to combine judgments from a group of experts. The Delphi Technique utilizes a series of well-defined questionnaire-based surveys, whereas Nominal Group Technique is a structured face-to-face meeting designed to facilitate consensus. Consensus-formation techniques require that each step build on the results of the previous steps. In this review, we describe these techniques, how they work, and their practical application in pediatric rheumatology, where they have been widely used to develop the outcome measures of several chronic rheumatic diseases, including juvenile idiopathic arthritis, rheumatoid arthritis, systemic lupus erythematosus, and idiopathic inflammatory myopathies, as well as the classification criteria for juvenile systemic sclerosis and juvenile vasculitides

20. SARMA PK, MISRA Ret AGGARWAL A: Physical disability, articular, and extra-articular damage in patients with juvenile idiopathic arthritis, Clin.Rheumatol., Vol. ., 2008
    Organism:Department of Immunology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, 226014, India
    Abstract:Data on outcome of juvenile idiopathic arthritis (JIA) from the Indian subcontinent is limited. Juvenile Arthritis Damage Index (JADI) is a newly proposed index which measures articular (JADI-A) and extra-articular damage (JADI-E). We studied the outcome of JIA using JADI in Indian patients. We assessed the damage in patients with JIA using JADI, and to see if JADI scores correlate with various parameters of damage and disease activity. We studied 89 patients of JIA (excluding enthesitis-related arthritis) with a >/=1-year duration of the disease. Besides JADI, clinical assessment included active joint count, joints with limited mobility, ESR, and CHAQ. Radiological damage was assessed according to the Dale scoring system. Correlation of JADI with various parameters was done by Spearman's rank correlation coefficient. The patient's distribution of JIA subtypes was polyarticular (47), systemic onset (SoJIA 23), oligoarticular (15), psoriatic arthritis (one) and others (three). The median duration of disease was 5 years (1-20). JADI-A ranged from 0-61 (Median 2); 60.7% of children had articular damage. Thirty-five (39.3%) patients had extra-articular damage; out of which, growth failure was the commonest. Persistent oligoarticular subtype had lesser JADI-A score as compared to SoJIA and polyarticular JIA. JADI-A correlated significantly with (p < 0.01) with radiological damage (0.538), CHAQ (0.567), JADI-E (0.513), duration of disease (0.385), and loss of education years due to disease (0.352). Further it also correlated with measures of disease activity like: ESR (0.286), duration of morning stiffness (0.258, p < 0.05), physician's global assessment (rS 0.623), and parent's global assessment (0.446), Almost two-thirds of patients with JIA had articular damage and one third had extra-articular damage. JADI is a good tool to measure damage in children with JIA

21. SYED RH, GILLIAM BEet MOORE TL: Rheumatoid factors and anticyclic citrullinated peptide antibodies in pediatric rheumatology, Curr.Rheumatol.Rep., Vol. 10(2), 156-163., 2008
    Organism:Division of Adult and Pediatric Rheumatology, Saint Louis University School of Medicine, Room 211A Doisy Hall, 1402 South Grand Boulevard, Saint Louis, MO 63104, USAFAU - Syed, Reema H
    Abstract:Juvenile idiopathic arthritis (JIA) is a heterogenous childhood disease without reliable biomarkers for monitoring disease progression. Immunoglobulin (Ig) M rheumatoid factor (RF) is used to define a subset of JIA patients, but its significance in JIA is dependent on the method of measurement. In addition to IgM RF, IgA RF has been implicated in determining disease severity in JIA, including functional disability and joint damage. Anticyclic citrullinated peptide (anti-CCP) antibodies have been a valuable diagnostic tool in rheumatoid arthritis, with varied results in their significance in JIA patients. Recent studies have demonstrated the possible usefulness of isotypes of anti-CCP antibodies in monitoring JIA patients to determine disease outcome. Overall, RF isotypes and anti-CCP isotypic antibodies have demonstrated increasing importance in the evaluation of JIA patients to determine which patients may have more aggressive or severe disease and to aid in possible treatment plans to prevent joint damage and disability

22. TAKADA H, ISHIMURA M, INADA H, OHGA S, KUSUHARA K, MOROI Y, FURUE Met HARA T: Lipopolysaccharide-induced monocytic cell death for the diagnosis of mild neonatal-onset multisystem inflammatory disease, J.Pediatr., Vol. 152(6), 885-7, 887., 2008
    Organism:Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan takadah@pediatrmedkyushu-uacjpFAU - Takada, Hidetoshi
    Abstract:In this report, we describe a boy who showed mild symptoms of neonatal-onset multisystem inflammatory disease. Although his symptoms and laboratory findings were similar to those of systemic juvenile idiopathic arthritis, further examinations revealed papilledema, meningitis, and a NLRP3 mutation. His peripheral blood monocytes died within 24 hours after lipopolysaccharide stimulation, a test that may be useful for diagnosis even in mild cases

23. TING TVet LOVELL DJ: Does early sulfasalazine treatment provide long-term benefits to patients with juvenile idiopathic arthritis?, Nat.Clin.Pract.Rheumatol., Vol. %20;., 2008
    Organism:TV Ting is a 2nd year Pediatric Rheumatology Fellow and DJ Lovell holds the Joseph E Levinson Chair in Pediatric Rheumatology and is the Associate Director of the Division of Rheumatology at Cincinnati Children's Hospital Medical Center in Cincinnati, OH, USA
    Abstract:The small, well-designed, observational study by van Rossum et al. raises and addresses questions of great significance for the treatment of children with JIA. The original RCT demonstrated significant benefits of sulfasalazine over placebo that, by today's standards, would be considered only moderate clinical improvement. Despite these initial modest effects, the sulfasalazine group demonstrated improved outcomes compared with the placebo group 9 years later

24. TYNJALA P, VAHASALO P, HONKANEN Vet LAHDENNE P: Drug survival of the first and second course of anti-TNF agents in juvenile idiopathic arthritis, Ann.Rheum.Dis., Vol. ., 2008
    Organism:Dpt of Pediatric Rheumatology, HUCH, Hospital for Children and Adolescents, Finland
    Abstract:OBJECTIVES: To evaluate drug survival (continuation rates on drug) of anti-TNF agents in juvenile idiopathic arthritis (JIA) and predictors for treatment discontinuation. METHODS: Retrospective observational study on JIA patients taking etanercept (n=105) or infliximab (n=104) with at least one-year follow-up. Kaplan-Meier curves and logrank statistics were used to compare treatments, and proportional hazards model to assess risk factors for discontinuation. RESULTS: Etanercept versus infliximab treatment survival was at 12 months 83% vs. 80%, at 24 months 68% vs. 68%, at 36 months 64% vs. 53%, at 48 months 61% vs. 48% (p=0.194), respectively. Reasons to discontinue the first biologic treatment were inefficacy (etanercept 28% vs. infliximab 20%, p=0.445), adverse events (7% vs. 22%, p=0.002) or inactive disease (10% vs. 16%, p=0.068). Females [hazard ratio (HR) 2.8, 95% confidence intervals (CI) 1.3 to 5.8], patients with systemic JIA (sJIA), HR 7.8 (95% CI 1.7 to 34.9) or those taking infliximab (HR 2.0, 95% CI 1.2-3.3) were in higher risk for treatment discontinuation. One-third of the patients were switched to the second anti-TNF therapy, which was discontinued less frequently than the first. At 12 months treatment survival of etanercept was 60%, infliximab 58%, and adalimumab 66% as the second-line anti-TNF therapy. CONCLUSIONS: Although infliximab was discontinued more often than etanercept because of adverse events, during a 48-month follow-up the overall treatment survival of etanercept and infliximab as the first biologic agent in JIA was comparable. A switch from one anti-TNF agent to another appears a reasonable therapeutic option

25. YOKOTA S: [Interleukin-6 as a pathogenic factor of systemic-onset juvenile idiopathic arthritis], Nihon Rinsho Meneki.Gakkai Kaishi., Vol. 31(2), 99-103., 2008
    Organism:Department of Pediatrics, Yokohama City University School of MedicineFAU - Yokota, Shumpei
    Abstract:Systemic-onset juvenile idiopathic arthritis (JIA) is a subtype of chronic childhood arthritis of unknown cause, manifested by spiking fever, erythematous rash, arthritis, pericarditis, and hepatosplenomegaly. It has been believed a disease developed due to an excessive production of pro-inflammatory cytokines, especially interleukin (IL)-6. We organized trials of a new biologic response modifier, Toclizimuab, anti-IL-6 receptor monoclonal antibody, to patients with systemic-onset JIA. Tocilizumab directs to solely IL-6 receptor, and is called as a one-point hit drug. We successfully administered Tocilizumab to stabilize the inflammation, and inflammatory symptoms and signs of the patients were abruptly gone. Previously, corticosteroids were the only life-saving drugs, but we proved Tocilizumab will be the possible alternative for treating these children. Basic science will help us to save the children, and clinical science also will promote the basic science in turn