Bibliography November2007

1. AUGUSTSSON J, EKSBORG S, ERNESTAM S, GULLSTROM Eet VAN VOLLENHOVEN R: Low-dose glucocorticoid therapy decreases risk for treatment-limiting infusion reaction to infliximab in patients with rheumatoid arthritis, Ann.Rheum.Dis., Vol. 66(11), 1462-1466., 2007
   Organism:Department of Rheumatology, Karolinska University Hospital Solna, 171 76 Stockholm, Sweden jennyaugustsson@apoteketseFAU - Augustsson, Jenny
   Abstract:BACKGROUND AND OBJECTIVE: Treatment-limiting infusion reactions to infliximab have not been fully explained in rheumatoid arthritis patients. Our main objective is to investigate the role of daily oral glucocorticoids use on such reactions. METHOD: Forty-three patients with immediate-type infusion reactions were identified in a large registry-based cohort. These patients were then compared with the entire cohort (n = 639) and, in a separate analysis, to a nested matched control group (n = 43). The following base-line variables were compared: use of oral glucocorticoids, health-assessment questionnaire, 28-joint count-based disease activity score, duration of disease and number of failed disease-modifying antirheumatic drugs. RESULTS: The proportion of infusions associated with infusion reactions decreased significantly during the study period (p = 0.0024). Fifty per cent of the patients in the cohort were treated with daily low-dose glucocorticoids at baseline. 15/326 (4.6%) patients had an infusion reaction as compared with 28/324 (8.6%) of patients without glucocorticoid treatment (p = 0.057). In the matched comparison, 15/43 (35%) of the cases were on low-dose glucocorticoids as compared with 27/43 (64%) of the controls (p = 0.017). The use of low-dose glucocorticoids was associated with a significantly lower risk for a treatment-limiting infusion reactions in a Kaplan-Meier analysis (p = 0.04). The number needed to treat to prevent a treatment-limiting infusion reaction was 25 (95% CI: 13 to 527) in the cohort. CONCLUSION: The use of daily low-dose glucocorticoids is associated with a lower risk for treatment-limiting infusion reactions to infliximab. Overall, treatment-limiting infusion reactions have become significantly less common during the past 5 years

2. BANDIN F, MERHENBERGER M, MODESTO A, BROCHARD Ket DECRAMER S: Steroid-responsive nephrotic syndrome in a child with juvenile idiopathic arthritis, Pediatr.Nephrol., Vol. ., 2007
   Organism:Department of Paediatric Nephrology, Children's Hospital, Centre de Reference du Sud-Ouest des Maladies Renales Rares, 31059, Toulouse, France, bandinf@chu-toulousefr
   Abstract:Renal disease is rare in children with juvenile idiopathic arthritis, although a number of associated nephropathies have been described, including mesangial glomerulonephritis. We report the presence of mesangial glomerulonephritis, revealed by a nephrotic syndrome, in a paediatric patient with juvenile idiopathic arthritis. Short-term steroid treatment induced a rapid remission of the nephrotic syndrome, but the presence of anti-nuclear antibodies, 1:320 in a homogeneous pattern, irregular deposits of C1q in a renal biopsy, and a mother with episodes of cutaneous lupus suggested an uncertain renal evolution for this infant

3. BRANDT HC, SPILLER I, SONG IH, VAHLDIEK JL, RUDWALEIT Met SIEPER J: Performance of referral recommendations in patients with chronic back pain and suspected axial spondyloarthritis, Ann.Rheum.Dis., Vol. 66(11), 1479-1484., 2007
   Organism:Rheumatology, Department of Medicine I, Charite Campus Benjamin Franklin, Berlin, GermanyFAU - Brandt, Henning Christian
   Abstract:BACKGROUND: Ankylosing spondylitis (AS) and its early form account for up to 5% of all patients with chronic back pain. Interest has recently focused on shortening the delay of 5-10 years between the appearance of first symptoms and the diagnosis of AS, particularly because effective treatments have now become available. Referral parameters that are easy for doctors in primary care to apply to patients presenting with possible AS could contribute to earlier diagnosis. METHODS: Orthopaedists and primary-care doctors were requested to refer patients with (1) chronic low back pain (duration >3 months) and (2) onset of back pain before <45 years of age to a specialist rheumatology outpatient clinic for further diagnostic investigation if at least one of the following screening parameters was present: (1) inflammatory back pain, (2) positive human leucocyte antigen B27, and (3) sacroiliitis detected by imaging. The final diagnosis was made according to expert opinion. RESULTS: In total, 350 referred cases were analysed. A diagnosis of definite axial spondyloarthritis (axial SpA), comprising established AS and pre-radiographic axial SpA, could be made in 45.4% of all referred patients (of which 50.3% were classified as AS and 49.7% as preradiographic axial SpA), whereas 45.4% were classified as non-SpA and 9.1% as possible SpA. A diagnosis of definite axial SpA could be made in 34.2% if only one referral parameter was positive, and in 62.6% if there was >1 positive referral parameter. CONCLUSIONS: The proposed referral parameters have proven useful when applied in primary care in identifying patients with AS/pre-radiographic axial SpA among young to middle-aged patients with chronic low back pain

4. CARROLL L, FRAZER IH, TURNER M, MARWICK THet THOMAS R: Receptor for advanced glycation end products Glycine 82 Serine polymorphism and risk of cardiovascular events in rheumatoid arthritis, Arthritis Res.Ther., Vol. 9(2), R39, 2007
   Organism:Diamantina Institute for Cancer, Immunology and Metabolic Medicine, University of Queensland, Princess Alexandra Hospital, Ipswich Road, Brisbane, Queensland 4102, Australia lisacarroll@iinetnetauFAU - Carroll, Lisa
   Abstract:Patients with rheumatoid arthritis (RA) are at risk of excess mortality, predominantly owing to cardiovascular (CV) events. The receptor for advanced glycation end products (RAGE) has been implicated in the perpetuation of the chronic inflammatory response in vascular disease. A Gly82-->Ser polymorphism in the RAGE gene, which is associated with enhanced RAGE signaling, is present more frequently in patients with RA than the general population. To investigate whether RAGE Gly82-->Ser polymorphism is associated with CV events in RA, we examined CV events, CV risk factors, features of RA and RAGE Gly82-->Ser polymorphism in 232 patients with RA attending a tertiary referral hospital. CV events, the duration and severity of RA, and risk factors for CV disease were determined using patient questionnaires, chart review, laboratory analysis and radiographs. DNA was typed for HLA-DRB1 genes and RAGE Gly82-->Ser polymorphism. The RAGE Ser82 allele, which is in linkage disequilibrium with the RA susceptibility allele HLA-DRB1*0401, was carried by 20% of patients. More than 20% of the cohort had suffered a vascular event; a shorter duration of RA, but not the RAGE genotype, was significantly associated with CV events. However, a history of statin use was protective. Thus, the RAGE Ser82 allele, associated with enhanced RAGE signaling, does not predispose to CV events in RA. However, treatment of hyperlipidemia with statins reduces the probability of a CV event

5. CEPUCH Get WORDLICZEK J: [Pain versus activity and fatigue in adolescents hospitalized because of cancer and rheumatoid diseases], Folia Med.Cracov., Vol. 47(1-4), 3-20., 2006
   Organism:Zaklad Pielegniarstwa Klinicznego, Instytut Pielegniarstwa i Poloznictwa Wydzilu Ochrony Zdrowia, Collegium Medicum Uniwersytetu Jagiellonskiego gcepuch@pocztaonetplFAU - Cepuch, Grazyna
   Abstract:INTRODUCTION: Chronic disease in adolescence is followed by many negative effects of somatic and psychosocial nature. These effects can be observed especially in oncological and rheumatologic diseases. This is due not only to the character of the disease, its chronic course, but also aggressive treatment. The objective of this work was to evaluate relationship between pain experience and sleep, fatigue and physical, social and intellectual functioning of teenage patients. MATERIAL AND METHODS: 124 adolescents, 14 to 20 years old, hospitalized because of cancer and juvenile rheumatoid arthritis participated in the study. Level of experienced pain was measured with VAS--Visual Analog Scale and NRS--Numeric Rating Scale. Quality of sleep was assessed with Polish version of Melzacks Questionnaire. Fatigue and activity were assessed with a questionnaire of our own construction. RESULTS: Pain was a significant symptom accompanying rheumatologic and oncological disease, although the sources of pain experience were different. Significant percentage of participants suffered from sleep disruption and activity impairment. An important relationship between increase of pain intensity and sleep disruption in oncological patients was found. Significant relationships between pain intensity vs. fatigue and also pain intensity vs. functioning were identified. CONCLUSIONS: Pain, fatigue and sleep disruption account for important factors in rheumatologic and oncological diseases. They also cause decrease in physical, social and mental functioning of teenage patients. Results show that there is a significant relationship between outcomes of disease, its treatment and impact on functioning and developmental course of adolescents. Care delivered to those patients must be integrated and involve multidisciplinary factors

6. CIVILIBAL M, CANPOLAT N, YURT A, KURUGOGLU S, ERDAMAR S, BAGCI O, SEVER L, KASAPCOPUR O, CALISKAN Set ARISOY N: A child with primary Sjogren syndrome and a review of the literature, Clin.Pediatr.(Phila)., Vol. 46(8), 738-742., 2007
   Organism:Department of Pediatric Nephrology, Istanbul University Cerrahpasa Medical Faculty, Istanbul, Turkey mcivilibal@gmailcomFAU - Civilibal, Mahmut
   Abstract:Primary Sjogren syndrome (pSS) is an uncommon disease in childhood. Childhood pSS might have different clinical manifestations than adult pSS. We describe a 13-year-old girl with multiple episodes of bilateral parotid swelling lasting 2 years. Her history included severe arthralgia, local edema, and purpura episodes since 9 years of age. During her 3-week hospitalization, 2 episodes of parotid swelling occurred, which both resolved in 48 hours. Ultrasonography and magnetic resonance images of parotid glands showed parenchymal inhomogeneity related to adipose degeneration and nodular pattern. Investigations showed elevated erythrocyte sedimentation rate, the presence of hypergammaglobulinemia, positive antinuclear antibody, and elevated rheumatoid factor, anti-Sjogren syndrome antigen A, and anti-Sjogren syndrome antigen B. Histopathologic examination of labial minor salivary glands revealed focal periductal lymphocytic infiltrate and sialoduct ectasia. She was diagnosed as having pSS. Recurrent parotid swelling is a more characteristic feature of disease in children, and this finding should alert the clinician to the possible diagnosis of pSS

7. CLUCAS AT, SHAH A, ZHANG YD, CHOW VFet GLADUE RP: Phase I evaluation of the safety, pharmacokinetics and pharmacodynamics of CP-481,715, Clin.Pharmacokinet., Vol. 46(9), 757-766., 2007
   Organism:Pfizer Global Research and Development, Groton/New London, Connecticut 06320, USAFAU - Clucas, Alan T
   Abstract:BACKGROUND AND OBJECTIVES: The chemokine receptor CCR1 is believed to play a role in several inflammatory diseases, primarily by promoting the migration of leukocytes through the endothelial barrier. Thus, a possible strategy for treating inflammatory diseases is inhibition of leukocyte infiltration by antagonising CCR1. Recently, CP-481,715 has been described as a potent and specific antagonist of CCR1. The aims of this study were to assess the safety, pharmacokinetics and pharmacodynamics of CP-481,715 along with drug interactions with ciclosporin. SUBJECTS AND METHODS: This was a phase I randomised, double-blind, placebo-controlled study with CP-481,715 in 78 healthy male volunteers. Subjects were administered escalating CP-481,715 doses of up to 3000 mg with food and after fasting in the single-dose study. In the drug interaction study, which was a single-dose, two-way crossover study, 12 subjects received a 300 mg dose of CP-481,715 as a suspension of polymorph A under fasted conditions, both with and without prior administration of ciclosporin. RESULTS AND CONCLUSIONS: All doses of CP-481,715 were well tolerated, with linear pharmacokinetics up to the 300 mg dose. The pharmacodynamic activity of CP-481,715 was detected ex vivo by demonstrating a dose-related and linear increase in the amount of macrophage inflammatory protein-1alpha, CCL3, required to induce CD11b upregulation. Analysis of vital signs indicated no consistent clinical effects, and statistical analysis of ECG characteristics demonstrated no significant prolongation of the corrected QT interval. A drug-drug interaction study with ciclosporin demonstrated that CP-481,715 clearance was decreased by ciclosporin, consistent with its ability to compete with P-glycoprotein. Phase II studies may be warranted to see if CP-481,715 exhibits efficacy in treating inflammatory diseases such as rheumatoid arthritis, multiple sclerosis or transplant rejection

8. DAS SK, PAREEK A, MATHUR DS, WANCHU A, SRIVASTAVA R, AGARWAL GGet CHAUHAN RS: Efficacy and safety of hydroxychloroquine sulphate in rheumatoid arthritis: a randomized, double-blind, placebo controlled clinical trial--an Indian experience, Curr.Med.Res.Opin., Vol. 23(9), 2227-2234., 2007
   Organism:Department of Rheumatology, CSM Medical University (formerly King George Medical College), Lucknow 226 003, IndiaFAU - Das, Siddharth Kumar
   Abstract:OBJECTIVE: Hydroxychloroquine (HCQ) has been used for a long time worldwide as a therapy for rheumatoid arthritis (RA). This trial was designed to determine whether HCQ was efficacious and safe in Indian patients with RA. RESEARCH DESIGN AND METHODS: The trial was a multicentre, placebo controlled, randomized and double-blind study. One hundred and twenty-two patients with RA were enrolled in 3 different centres for the trial (26 males and 96 females in the age group of 18-60 years). Patients were randomized to receive either hydroxychloroquine tablets (n = 61) two tablets of 200 mg daily or placebo (n = 61) two tablets daily. After 8 weeks all patients received one tablet of hydroxychloroquine 200 mg daily for 4 weeks. Every patient also received one tablet of Nimesulide 100 mg twice daily. MAIN OUTCOME MEASURES: Assessment of response at 12 weeks using modified ACR 20 (American College of Rheumatology 20) criteria where Health Assessment Questionnaire (HAQ) was replaced by ARA (American Rheumatology Association) functional class. RESULTS: 40.4% of patients on hydroxychloroquine showed improvement by modified ACR response criteria whereas only 20.7% (p = 0.02) showed improvement in the placebo group. No significant side effects were observed in any of the patients. There were no ocular toxicities. CONCLUSIONS: Hydroxychloroquine was found to be an effective and well-tolerated drug in rheumatoid arthritis in Indian patients

9. DE BENEDETTI Fet RAVELLI A: Juvenile Idiopathic Arthritis: Will Etanercept be an Improvement over Current Therapies?, BioDrugs., Vol. 14(2), 93-98., 2000
   Organism:Dipartimento di Scienze Pediatriche, Universita degli Studi di Pavia, IRCCS Policlinico San Matteo, Pavia, ItalyFAU - De Benedetti, F
   Abstract:Overexpression of cytokines in inflamed joints plays an important role in joint inflammation and in damage to articular tissue. Biological agents aimed at specifically antagonising tumour necrosis factor (TNF) are effective in the treatment of adult rheumatoid arthritis. A recent trial of etanercept, a genetically engineered fusion protein consisting of the Fc domain of human IgG1 and the TNF receptor p75, has demonstrated that this agent is also well tolerated and effective in patients with juvenile idiopathic arthritis (JIA). Etanercept offers a promising new alternative for patients with JIA who have persistently active arthritis despite treatment with methotrexate. Further studies are needed to clarify whether etanercept is equally effective in the various onset types of JIA (oligoarthritis, polyarthritis and systemic arthritis), whether it can modify disease progression and whether it can be administered safely for long periods of time to children

10. DYER JA, GUITART J, KLEIN-GITELMAN Met MANCINI AJ: Neutrophilic panniculitis in infancy: a cutaneous manifestation of juvenile rheumatoid arthritis, J.Am.Acad.Dermatol., Vol. 57(5 Suppl), S65-S68, 2007
    Organism:Division of Dermatology, Children's Memorial Hospital, Chicago, Illinois, USA DyerJA@healthmissourieduFAU - Dyer, Jon A
    Abstract:Neutrophilic panniculitis is rare and is classified as a panniculitic member of the neutrophilic dermatoses spectrum. In affected patients, an underlying systemic disease, such as myelodysplasia, is often present. We describe an infant with juvenile rheumatoid arthritis who developed neutrophilic panniculitis. Neutrophilic panniculitis clinically mimics other panniculitides and biopsy specimen can be diagnostic. Identification of this entity can aid the diagnosis of the underlying systemic process

11. FRAMPTON JEet KEATING GM: Celecoxib : a review of its use in the management of arthritis and acute pain, Drugs., Vol. 67(16), 2433-2472., 2007
    Organism:Wolters Kluwer Health | Adis, Auckland, New Zealand, an editorial office of Wolters Kluwer Health, Conshohocken, Pennsylvania, USAFAU - Frampton, James E
    Abstract:Celecoxib (Celebrex((R))), the first cyclo-oxygenase (COX) 2-selective inhibitor (coxib) to be introduced into clinical practice, has been available for almost a decade. It is approved in one or more countries worldwide for the relief of the signs and symptoms of osteoarthritis (OA), rheumatoid arthritis (RA), juvenile rheumatoid arthritis (in patients aged >/=2 years) and ankylosing spondylitis (AS), the management of acute pain in adults, the treatment of primary dysmenorrhoea and the reduction in the number of adenomatous colorectal polyps in familial adenomatous polyposis.Celecoxib remains an effective and useful altenative to nonselective NSAIDs in the treatment of acute or chronic musculoskeletal pain. In the latter setting, it offers the prospect of improved gastrointestinal (GI) tolerability and, in patients not taking aspirin for cardioprophylaxis, a GI safety advantage. Currently available evidence of an increase in cardiovascular (CV) risk with celecoxib is inconsistent; any increase in risk is likely to be small and similar to that with nonselective NSAIDs. As with all NSAIDs, the potential GI, CV and renal risks of celecoxib must be weighed against the potential benefits in each individual; it is a rational choice for patients at low CV risk who require NSAID therapy, especially those at increased risk of NSAID-induced GI toxicity, but also those unresponsive to, or intolerant of, other NSAIDs. If selected, celecoxib, like all NSAIDs, should be used at the lowest effective dose for the shortest possible duration

12. GARCIA-CARRASCO M, FUENTES-ALEXANDRO S, ESCARCEGA RO, ROJAS-RODRIGUEZ Jet ESCOBAR LE: Efficacy of thalidomide in systemic onset juvenile rheumatoid arthritis, Joint Bone Spine., Vol. 74(5), 500-503., 2007
    Organism:Systemic Autoimmune Diseases Research Unit, HGZ #36, CMN Manuel Avila Camacho, Instituto Mexicano del Seguro Social, Puebla, Mexico 30591mgc@combesFAU - Garcia-Carrasco, Mario
    Abstract:Thalidomide is an immunomodulating agent which reverses many of the cytokine disturbances seen in systemic onset juvenile idiopathic arthritis (SoJIA) with inadequate response to other treatments. We report 3 cases of recalcitrant SoJIA which improved dramatically after treatment with thalidomide. PATIENTS: Three children aged 9, 8, and 6 years diagnosed with SoJIA treated with conventional therapy including NSAIDs, corticosteroids, methotrexate and etanercept failed to respond fully and their condition worsened. Thalidomide was begun based on two previous reports showing its efficacy in recalcitrant SoJIA. RESULTS: Thalidomide produced successful remission of the disease in all 3 patients according to the preliminary criteria for inactive disease and clinical remission of JIA. CONCLUSION: Thalidomide may be a viable, alternative corticoid-sparing therapy in patients with recalcitrant, multidrug-resistant SoJIA

13. GERLONI V, PONTIKAKI I, GATTINARA Met FANTINI F: Focus on adverse events of TNF{alpha} blockade in JIA in an open monocentric long-term prospective study of 163 patients, Ann.Rheum.Dis., Vol. ., 2007
    Organism:Gaetano Pini Institute of orthopedic, Italy
    Abstract:OBJECTIVE: To report adverse events (AEs) seen in a large cohort of patients with Juvenile Idiopathic Arthritis (JIA) treated with TNFalpha blockers (Infliximab and Etanercept). METHODS: All JIA patients treated with Infliximab or Etanercepet at the Paediatric Rheumatologic Centre of the G. Pini Institute (Milan) from November 1999 to February 2006, were enrolled in an open, monocenter, long-term prospective study. RESULTS: 163 patients (68 Infliximab, 95 Etanercept) were enrolled. Mean onset age 6.4+/-4.8 years, mean age 17.19.2 years, mean therapy duration 22.9+/-17.6 months. 45 patients (32 Infliximab, 13 Etanercept) failed to respond to or did not tolerate the first biologic and switched to a second one. 208 treatments (81 Infliximab, 127 Etanercept) were done. 71 AEs occurred in 51 (62.9%) Infliximab patients and led to discontinuation in 26 (32.1%). 133 AEs occurred in 69 (54.3%) Etanercept patients and led to discontinuation in 18 (14.2%). Some AEs, such as thrombocytopenia, neuro-psychiatric disorders, new onset of Crohn's disease, new onset or flare-up of chronic iridocyclitis (CIC), are unusual and have rarely been described before, yet proved to be significant in frequency and/or clinically noteworthy in the large population we followed. CONCLUSIONS: In our six-year experience, anti-TNFalpha agents Infliximab and Etanercept have been well-tolerated and safe, and may be associated with only few serious, but all reversible, AEs. However, such inhibitors are associated with various and numerous AEs. Children and young adults affected by JIA should be carefully monitored so as to limit the risk of AEs during anti-TNFalpha therapy as much as possible

14. HARDIN DS, KEMP SFet ALLEN DB: Twenty years of recombinant human growth hormone in children: relevance to pediatric care providers, Clin.Pediatr.(Phila)., Vol. 46(4), 279-286., 2007
    Organism:Ohio State University and Columbus Children's Hospital, Columbus, OH 43205, USA hardind@pediatricsohio-stateeduFAU - Hardin, Dana S
    Abstract:Recombinant human growth hormone has revolutionized the management of children and adolescents with growth hormone deficiency and other growth disorders, but clinical and ethical controversies remain regarding diagnostic approach, optimal recombinant human growth hormone dose and duration, and expected outcomes. Management of pubertal and transitioning patients with growth hormone deficiency has also commanded increased attention. Recent clinical studies that demonstrate the positive health benefits of recombinant human growth hormone in children with cystic fibrosis, inflammatory bowel disease, and juvenile rheumatoid arthritis have not yet clarified issues about patient selection and appropriate long-term use. An understanding of current recombinant human growth hormone indications and controversies can facilitate patient evaluation and expedite referral for potential treatment. This review summarizes current indications for recombinant human growth hormone use, discusses clinical challenges, and provides recommendations for pediatricians caring for children who may be appropriate candidates for recombinant human growth hormone therapy

15. HWA V, CAMACHO-HUBNER C, LITTLE BM, DAVID A, METHERELL LA, EL KHATIB N, SAVAGE MOet ROSENFELD RG: Growth hormone insensitivity and severe short stature in siblings: a novel mutation at the exon 13-intron 13 junction of the STAT5b gene, Horm.Res., Vol. 68(5), 218-224., 2007
    Organism:Department of Pediatrics, Oregon Health and Sciences University, Portland, OR 97239-3098, USAFAU - Hwa, Vivian
    Abstract:BACKGROUND/AIMS: Growth hormone insensitivity (GHI) is characterized by severe short stature, high serum growth hormone (GH), low serum IGF-I and IGFBP-3 levels and is classically associated with genetic defects of the GH receptor (GHR). Recently, mutations of the STAT5b gene have been identified and shown to be associated with GHI and severe IGF deficiency. We investigated 2 sisters from a consanguineous family from Kuwait, with clinical and biochemical features of GHI, in whom no molecular defects in the GHR were identified. METHODS: Serum and DNA were analyzed. RESULTS: In addition to GHI, siblings 2 and 1 presented with, respectively, a diagnosis of juvenile idiopathic arthritis and recurrent pulmonary infections. Molecular analysis of the STAT5b gene revealed a novel homozygous deletion of a G at the junction of exon 13-intron 13. The parents, who are of normal height, were heterozygous for the mutation. CONCLUSIONS: This is the first STAT5b defect to be identified in siblings, further supporting the autosomal recessive mode of transmission of STAT5b deficiency. The results affirm that defective STAT5b is an etiology for IGF deficiency and the GHI phenotype, and emphasize the importance of considering this diagnosis in patients with IGF deficiency, especially when associated with diverse immunological problems

16. ISAACS JD: T cell immunomodulation--the Holy Grail of therapeutic tolerance, Curr.Opin.Pharmacol., Vol. 7(4), 418-425., 2007
    Organism:Wilson Horne Immunotherapy Centre and Musculoskeletal Research Group, Institute of Cellular Medicine, Catherine Cookson Building, Framlington Place, Newcastle-upon-Tyne NE2 4HH, United Kingdom jdisaacs@nclacukFAU - Isaacs, John D
    Abstract:The concept and practice of therapeutic tolerance has successfully been applied to animal models of autoimmunity and transplantation for more than 2 decades. Finally, there are encouraging signs of its translation to clinical practice. Short courses of anti-CD3 monoclonal antibody therapy have provided lasting benefits in recent-onset type 1 diabetes in association with evidence for the induction of immunoregulatory mechanisms. Co-stimulation blockade with abatacept (CTLA4-Ig) will soon be licensed for the treatment of rheumatoid arthritis - over the past year phase III studies have demonstrated impressive improvement in subjective and objective signs of the disease. T cell depletion is in development for several conditions, again with recent studies demonstrating evidence of immune regulation in some instances. More specific antigen-directed peptide therapies have also been applied to atopic asthma, type 1 diabetes, and adult and juvenile arthritis. The tragic sequelae of the phase I trial of TGN1412 at Northwick Park demonstrated the delicate, but unpredictable, therapeutic ratio of some T-cell-directed treatments and, in the UK, have led to new guidelines for early-phase clinical trials of immune-directed therapies

17. JOHANSEN H, ANDRESEN IL, NAESS EEet HAGEN KB: Health status of adults with short stature: a comparison with the normal population and one well-known chronic disease (rheumatoid arthritis), Orphanet.J.Rare.Dis., Vol. 2, 10, 2007
    Organism:Sunnaas Rehabilitation Hospital, TRS Resource Centre for Rare Disorders, 1450 Nesoddtangen, Norway heidijohansen@sunnaasnoFAU - Johansen, Heidi
    Abstract:BACKGROUND: To examine the subjective health status of adults with short stature (ShSt) and compare with the general population (GP) and one well-known chronic disease, rheumatoid arthritis (RA). In addition, to explore the association between age, gender, height, educational level and different aspects of health status of adults with short stature. METHODS: A questionnaire was mailed to 72 subjects with short stature registered in the database of a Norwegian resource centre for rare disorders, response rate 61% (n = 44, age 16-61). Health status was assessed with SF-36 version 2. Comparison was done with age and gender matched samples from the general population in Norway (n = 264) and from subjects with RA (n = 88). RESULTS: The ShSt sample reported statistically significant impaired health status in all SF-36 subscales compared with the GP sample, most in the physical functioning, Mean Difference (MD) 34 (95% Confidence Interval (CI) 25-44). The ShSt reported poorer health status in mental health, MD 11 (95% CI 4-18) and social functioning, MD 11 (95% CI 2-20) but better in role physical MD 13 (95% CI 1-25) than the RA sample. On the other subscales there were minor difference between the ShSt and the RA sample. Within the short stature group there was a significant association between age and all SF-36 physical subcales, height was significantly associated with physical functioning while level of education was significantly associated with mental health. CONCLUSION: People with short stature reported impaired health status in all SF-36 subscales indicating that they have health problems that influence their daily living. Health status seems to decline with increasing age, and earlier than in the general population

18. KAKATI P, SODHI KS, SANDHU MS, SINGH S, KATARIYA Set KHANDELWAL N: Clinical and ultrasound assessment of the knee in children with juvenile rheumatoid arthritis, Indian J.Pediatr., Vol. 74(9), 831-836., 2007
    Organism:Department of Radiodiagnosis, Postgraduate Institute of Medical Education and Research, Chandigarh, IndiaFAU - Kakati, Pratap
    Abstract:OBJECTIVE: To correlate clinical features with ultrasound (USG) findings in the detection, quantification and follow up of inflammatory signs of knee in children with mono or pauciarticular juvenile rheumatoid arthritis (JRA). METHODS: Thirty patients (11 girls, 19 boys) with pauciarticular JRA (14 with monoarticular and 16 with bilateral knee involvement) were studied. Mean disease duration was 10 months (range 2 months to 5 yr). All knees were classified into two groups, according to the presence or absence of acute inflammation. Clinical assessment and ultrasound was done in all patients on the same day. All the patients received naproxen (15-20 mg/Kg/day) for a period of six months, after which clinical assessment and ultrasound study was repeated. RESULTS: Synovial proliferation and effusion, was demonstrated in a much higher frequency in those clinically active (Group A) as compared to these in clinical remission (Group B). Statistically significant differences between clinical and USG indices were seen. CONCLUSION: USG of knee is more sensitive than clinical assessment in detection of synovial effusion and thickening and plays a useful role in monitoring evolution of the inflammatory process, its quantification and for follow up

19. KAWASHIMA H, SATO A, NISHIMATA S, YAMADA N, KASHIWAGI Y, WATANABE K, TAKEKUMA K, HOSHIKA Aet OZAWA T: A case report of neonatal onset multisystemic inflammatory disease in Japan treated with continuous hemodiafiltration and steroid pulse therapy, Ther.Apher.Dial., Vol. 11(3), 232-234., 2007
    Organism:Department of Pediatrics, Tokyo Medical University, Tokyo, Japan hisashi@tokyo-medacjpFAU - Kawashima, Hisashi
    Abstract:Neonatal onset multisystem inflammatory disease (NOMID), which is also known as chronic infantile neurological cutaneous and articular syndrome, is a rare disease that is characterized by the triad of cutaneous rash, chronic meningitis and arthropathy. The long-term prognosis is poor, with progressive deafness and visual impairment, and worsening of the central nervous system manifestations. Some fatal cases have been reported secondary to infection, vasculitis and amyloidosis. We recently managed a typical case of NOMID where the combined treatment of continuous hemodiafiltration and steroid pulse therapy was effective. The patient showed repeated flare ups of fever, arthralgia and meningitis accompanied with high levels of cytokines. The effect was temporary, but useful in recovery from such a serious condition

20. KHALKHALI-ELLIS Z, MOORE TLet HENDRIX MJ: Could hormones make a difference in the treatment of juvenile rheumatoid arthritis?, BioDrugs., Vol. 13(2), 77-86., 2000
    Organism:Department of Anatomy and Cell Biology, The University of Iowa, Iowa City, Iowa, USAFAU - Khalkhali-Ellis, Z
    Abstract:Adrenal androgens dehydroepiandrosterone (DHEA; prasterone) and its sulphated form (DHEA-S) are among the most abundant hormonal steroids in men and nonpregnant women. Deficiencies of these adrenal androgens are associated with autoimmune disorders such as rheumatoid arthritis (RA). Recent studies from our laboratory have also identified low levels of adrenal androgens in the serum and synovial fluid of patients with juvenile rheumatoid arthritis (JRA). These findings support and complement those already published for RA and other autoimmune diseases. Because of the paucity of data on the hormonal status of patients with JRA, studies on the relationship between hypoandrogenicity and predisposition to develop JRA, and/or disease progression have not been conducted. In addition, despite the rapid expansion of research in the clinical use of these adrenal androgens in hyperlipidaemia, atherosclerosis, obesity, diabetes mellitus, insulin resistance and hypertension, their potential beneficial effects in JRA/RA have not been fully investigated. In fact, clinical trials of adrenal androgens in RA have only been conducted for the treatment of systemic lupus erythematosus. Further studies using prospective approaches are necessary to provide a unified consensus on the hormonal status of patients with JRA (as well as those with RA). This overview of our knowledge of the putative role(s) of hormones in arthritis will hopefully stimulate researchers in basic science and rheumatologists to synergistically collaborate in the effective translation of such knowledge to new clinical approaches

21. KIMURA E, OGA Set PEREIRA RM: Comparative study of the pharmacokinetics of MTX in juvenile idiopathic arthritis patients receiving long-term MTX monotherapy or MTX plus chloroquine, J.Clin.Pharm.Ther., Vol. 32(6), 579-584., 2007
    Organism:Department of Pharmacy and Pharmacology, State University of Maringa, Parana, BrazilFAU - Kimura, E
    Abstract:Objective: To compare the pharmacokinetics and report on the clinical effects of methotrexate (MTX) in patients with juvenile idiopathic arthritis (JIA), receiving long-term MTX or MTX plus chloroquine (CQ). Methods: The pharmacokinetics of MTX, clinical characteristics (morning stiffness, joint tenderness and number of swollen joints) and biochemical markers (A-amyloid substance, C-reactive protein, erythrocyte sedimentation rate, fibrinogen and alpha-glycoprotein acid, alanine transaminase and aspartate transaminase) of the JIA patients were determined. Eight patients were treated with MTX (0.15 mg/kg) and another eight with MTX (0.15 mg/kg) plus CQ (4 mg/kg) for at least 6 months. Results: All patients had polyarticular involvement and the clinical characteristics and biochemical markers were similar for the two groups. The pharmacokinetics of MTX were also similar with the C(max) and AUC values being 455.00 +/- 101.00 nm and 1469.92 +/- 299.77 nm/h for MTX group and 425.00 +/- 169.60 nm and 1560.73 +/- 615.49 nm/h for MTX plus CQ group, respectively. The respective creatinine clearance was 117.95 +/- 12.58 for MTX group and 99.17 +/- 22.65 mL/min for MTX plus CQ. Conclusion: The pharmacokinetics of MTX in JIA patients treated chronically with MTX are similar, with or without CQ co-treatment

22. MAHEVAS M, VAIDA I, LE PAGE L, SID-IDRIS S, ROYER B, GAREDI R, DAMAJ G, DUHAUT P, CLAISSE JF, DUCROIX JPet MAROLLEAU JP: [Haematopoietic stem cell transplantation in the treatment of autoimmune diseases.], Rev.Med.Interne., Vol. ., 2007
    Organism:Service de medecine interne, hopital Nord, CHU d'Amiens, place Victor-Pauchet, 80054 Amiens cedex 1, France
    Abstract:PURPOSE: During the past ten years, more than 1000 patients suffering from severe autoimmune disease have received an autologous haematopoietic stem cell transplant. These new therapeutic have been used in systemic sclerosis (scleroderma), multiple sclerosis, rheumatoid arthritis, juvenile idiopathic arthritis and systemic lupus erythematosus. CURRENT KNOWLEDGE AND KEY POINTS: Autologous haematopoietic stem cell transplantation has become a curative option for condition with very poor prognosis as severe systemic sclerosis, lupus erythematosus or other systemic diseases. This review summarizes the current experience in the phase I and II clinical trials in Europe and North America. We describe the main results and the limits of stem cell transplantation in systemic diseases. FUTURE PROSPECTS AND PROJECTS: Autologous haematopoietic stem cell transplant in the treatment of autoimmune disease has evolved from a experimental concept to a clinically feasible and powerfull therapy for selected patients with severe disease

23. MARINOU I, MONTGOMERY DS, DICKSON MC, BINKS MH, MOORE DJ, BAX DEet WILSON AG: The interferon induced with helicase domain 1 A946T polymorphism is not associated with rheumatoid arthritis, Arthritis Res.Ther., Vol. 9(2), R40, 2007
    Organism:Section of Musculoskeletal Sciences, School of Medicine & Biomedical Sciences, The University of Sheffield, Royal Hallamshire Hospital, Sheffield S10 2RX, UK mdp04im@sheffieldacukFAU - Marinou, Ioanna
    Abstract:An important feature of autoimmune diseases is the overlap of pathophysiological characteristics. Clustering of autoimmune diseases in families suggests that genetic variants may contribute to autoimmunity. The aim of the present study was to investigate the role of the interferon induced with helicase domain 1 (IFIH1) A946T (rs1990760 A>G) variant in rheumatoid arthritis (RA), as this was recently associated with susceptibility to type 1 diabetes. A total of 965 Caucasians with RA and 988 healthy controls were genotyped for IFIH1 A946T. Gene expression of IFIH1 was measured in peripheral blood leukocytes using real-time PCR. Genotypes were equally distributed in both RA cases and healthy controls (odds ratio for allele C = 0.9, 95% confidence interval = 0.8-1.0, P = 0.3). No association was detected after stratification by sex, age at onset, rheumatoid factor status, anti-cyclic citrullinated peptide status or radiological joint damage. Levels of IFIH1 mRNA were approximately twofold higher in blood leucocytes of RA cases compared with healthy controls (P < 0.0001). These results indicate that the IFIH1 is upregulated in RA but that the A946T variant does not contribute significantly to the genetic background of RA

24. MARTINEZ A, OROZCO G, VARADE J, SANCHEZ LM, PASCUAL D, BALSA A, GARCIA A, DE LA CONCHA EG, FERNANDEZ-GUTIERREZ B, MARTIN Jet URCELAY E: Macrophage migration inhibitory factor gene: influence on rheumatoid arthritis susceptibility, Hum.Immunol., Vol. 68(9), 744-747., 2007
    Organism:Department of Clinical Immunology, Hospital Clinico San Carlos, Madrid, SpainFAU - Martinez, Alfonso
    Abstract:The macrophage inhibitory factor (MIF) is a cytokine that has been implicated in several inflammatory and autoimmune diseases, including rheumatoid arthritis, systemic lupus, glomerulonephritis, and multiple sclerosis. In rheumatoid arthritis (RA), results ranging from lack of association of MIF polymorphisms with RA, to involvement in either severity or susceptibility to the disease have been reported in the past. We aimed at investigating the role of this gene in RA in the Spanish population. Two well-known MIF promoter polymorphisms were tested in 606 adult RA patients and 886 healthy controls: a single nucleotide polymorphism at -173G/C and a tetranucleotide repeat (CATT)(5-8) located at -794. We found a significant association of the allele -173C with RA (p = 0.01; odds ratio [OR] = 1.31; 95% confidence interval [CI] = 1.06-1.62). The -173C risk allele, previously reported to be transmitted in excess in patients with juvenile idiopathic arthritis, was significantly more frequent in early-onset adult RA patients than in healthy controls (p = 0.003; OR = 1.57; 95% CI = 1.14-2.15), whereas late-onset patients were not significantly different to controls (p = 0.6; OR = 1.09; 95% CI = 0.77-1.55). In conclusion, the -173C allele in the MIF promoter region is associated with increased RA predisposition, mainly in early-onset patients

25. MOLL C, HERNANDEZ MV, CANETE JD, GOMEZ-PUERTA JA, SORIANO A, COLLADO Aet SANMARTI R: Ilium Osteitis as the Main Manifestation of the SAPHO Syndrome: Response to Infliximab Therapy and Review of the Literature, Semin.Arthritis Rheum., Vol. ., 2007
    Organism:Arthritis Unit, Rheumatology Department, Hospital Clinic, University of Barcelona, Barcelona, Spain
    Abstract:OBJECTIVE: To analyze the clinical efficacy of anti-tumor necrosis factor (TNF)-alpha therapy in the SAPHO (synovitis, acne, pustulosis, hyperostosis, osteitis) syndrome. We describe 2 new cases with ilium osteitis as the main SAPHO syndrome feature and review reported cases treated with anti-TNF-alpha. METHODS: A literature search of SAPHO syndrome cases treated with TNF-alpha blocking therapy with special emphasis on osteoarticular and skin responses was performed. RESULTS: Eighteen cases were identified: 17 SAPHO syndrome and 1 chronic recurrent multifocal osteomyelitis, a juvenile variant of SAPHO syndrome. Sixteen were reported cases and 2 were nonreported cases seen in our arthritis unit. Sixteen patients received infliximab and 2 received etanercept, with an early, sustained clinical improvement in most cases. CONCLUSIONS: Anti-TNF-alpha therapies are effective treatment for patients with refractory SAPHO syndrome, not only for cutaneous lesions but also for persistent bone lesions such as osteitis

26. OSSENDORF C, KAPS C, KREUZ PC, BURMESTER GR, SITTINGER Met ERGGELET C: Treatment of posttraumatic and focal osteoarthritic cartilage defects of the knee with autologous polymer-based three-dimensional chondrocyte grafts: 2-year clinical results, Arthritis Res.Ther., Vol. 9(2), R41, 2007
    Organism:Department of Traumotology and Orthopaedic Surgery, University of Freiburg, Hugstetter Strasse 55, 79106 Freiburg, Germany cossendorf@researchbalgristchFAU - Ossendorf, Christian
    Abstract:Autologous chondrocyte implantation (ACI) is an effective clinical procedure for the regeneration of articular cartilage defects. BioSeed-C is a second-generation ACI tissue engineering cartilage graft that is based on autologous chondrocytes embedded in a three-dimensional bioresorbable two-component gel-polymer scaffold. In the present prospective study, we evaluated the short-term to mid-term efficacy of BioSeed-C for the arthrotomic and arthroscopic treatment of posttraumatic and degenerative cartilage defects in a group of patients suffering from chronic posttraumatic and/or degenerative cartilage lesions of the knee. Clinical outcome was assessed in 40 patients with a 2-year clinical follow-up before implantation and at 3, 6, 12, and 24 months after implantation by using the modified Cincinnati Knee Rating System, the Lysholm score, the Knee injury and Osteoarthritis Outcome Score, and the current health assessment form (SF-36) of the International Knee Documentation Committee, as well as histological analysis of second-look biopsies. Significant improvement (p < 0.05) in the evaluated scores was observed at 1 and/or 2 years after implantation of BioSeed-C, and histological staining of the biopsies showed good integration of the graft and formation of a cartilaginous repair tissue. The Knee injury and Osteoarthritis Outcome Score showed significant improvement in the subclasses pain, other symptoms, and knee-related quality of life 2 years after implantation of BioSeed-C in focal osteoarthritic defects. The results suggest that implanting BioSeed-C is an effective treatment option for the regeneration of posttraumatic and/or osteoarthritic defects of the knee

27. POUREL J: [Clinical diagnosis of Lyme borreliosis in case of joint and muscular presentations], Med.Mal Infect., Vol. 37(7-8), 523-531., 2007
    Organism:Service de rhumatologie et UMR CNRS 7561, CHU de Nancy, rue du Morvan, 54511 Vandoeuvre-les-Nancy cedex, France jpourel@chu-nancyfrFAU - Pourel, J
    Abstract:The diagnosis of Lyme borreliosis in case of joint and muscular presentations is generally suggested by epidemiological factors. However, as a rule, laboratory testing is required to confirm the diagnosis. When considering the epidemiology of Lyme borreliosis in France, the only areas free of ticks infected by Borrelia burgdorgeri sl, are those close to the Mediterranean sea or at high altitude. The risk is greatest in the Alsace region. Exposure is particularly high among forest workers and people who use the countryside for their leisure activities. The likelihood of infection following a tick bite is difficult to assess; indeed, the bite site may remain unnoticed. A medical history of erythema migrans, if untreated, is a major diagnostic clue, although the association appears to be less consistent in France than in the US. Lyme arthritis generally arises apparently spontaneously. It is characteristically mono- or oligo-articular, asymmetrical, predominantly affects the knee, and has an intermittent course. Synovial cysts and enthesitis are common. Myositis is rare, polymorphic, and has been linked to other symptoms in the same localizations. Minor arthralgia and myalgia frequently occur, principally early in the course of the infection. It was suggested that sequels of the disease include so-called fibromyalgic syndromes. The principal differential diagnosis as far as arthritis is concerned, is made on spondylarthropathy and chronic juvenile arthritis. Rheumatoid arthritis is another pathology, although Lyme arthritis does sometimes evolve to chronicity

28. PRIEUR AMet QUARTIER P: Comparative tolerability of treatments for juvenile idiopathic arthritis, BioDrugs., Vol. 14(3), 159-183., 2000
    Organism:Department of Paediatric Immunohaematology and Paediatric Rheumatology, Hopital Necker-Enfants Malades, Paris, FranceFAU - Prieur, A M
    Abstract:Juvenile idiopathic arthritis (JIA) includes several forms of chronic arthritis in children. Treatments are chosen according to the type and severity of the disease. Nonsteroidal anti-inflammatory drugs (NSAIDs) and corticosteroids remain the mainstays of therapy. Traditional slower acting anti-rheumatic drugs, such as gold therapy, penicillamine, sulfasalazine, tiopronin and hydroxychloroquine, are usually poorly active in children. In addition, adverse effects are common, including severe macrophage activation syndrome with gold therapy or sulfasalazine. Low dose, once weekly methotrexate has emerged as the therapeutic agent of choice for children who fail to respond adequately to the administration of an NSAID, especially in those with the extended oligoarticular subtype of the disease. Other immunosuppressive agents, such as cyclosporin, are sometimes combined with methotrexate. In recent years, novel treatments have been developed. Autologous hematopoietic stem cell transplantation is effective in a number of children with severe JIA, whose disease has been refractory to conventional therapy. However, only short term follow-up data are currently available for this novel therapy. In addition, severe infections complicated by macrophage activation syndrome and death have been reported. Finally, anti-tumour necrosis factor-alpha therapy has shown efficacy in more than two-thirds of children with JIA and polyarthritis, and other cytokine inhibitors may be soon available

29. RUSSO RA, ROSENZWEIG SDet KATSICAS MM: Hepatitis A-Associated Macrophage Activation Syndrome in Children with Systemic Juvenile Idiopathic Arthritis: Report of 2 Cases, J.Rheumatol., Vol. ., 2007
    Organism:From Servicio de Inmunologia y Reumatologia, Hospital de Pediatria "Prof Dr Juan P Garrahan," Buenos Aires, Argentina
    Abstract:OBJECTIVE: We describe two 3-year-old patients with systemic juvenile idiopathic arthritis (SJIA) who developed hepatitis A-associated macrophage activation syndrome (MAS). One patient showed MAS as the presenting manifestation of SJIA, while MAS complicated SJIA during the second year of the disease course in the other child. Both girls presented with fever, jaundice, hepatosplenomegaly, neurological involvement, mucosal hemorrhage, and purpura. Cytopenias, hypofibrinogenemia, and hemophagocytosis confirmed the diagnosis. After aggressive treatment with high-dose corticosteroids and immunosuppressants one patient entered remission while the other one died. Hepatitis A virus may induce severe MAS in SJIA

30. SHANMUGAVEL C, SODHI KS, SANDHU MS, SIDHU R, SINGH S, KATARIYA Set KHANDELWAL N: Role of Power Doppler sonography in evaluation of therapeutic response of the knee in juvenile rheumatoid arthritis, Rheumatol.Int., Vol. ., 2007
    Organism:Department of Radiodiagnosis, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, 160012, India, sodhiks@rediffmailcom
    Abstract:The objective is to study the role of power Doppler sonography (PDS) in assessment of therapeutic response in juvenile rheumatoid arthritis (JRA) of knee joint. Thirty patients (age range 3-11 years) of JRA with knee joint involvement were selected for this study. Clinical assessment and ultrasound was done on the same day and repeated at the end of second and sixth month of therapy. All patients received naproxen (15-20 mg/kg/day) for a period of 6 months. Total clinical score (TCS) was calculated as sum of scores of pain, articular swelling and functional impairment. PDS was performed and degree of vascularity was assessed and graded. Total USG score was obtained by adding sum of scores of synovial effusion, synovial thickening and PDS. Results were compared between the total clinical score and the total ultrasound score and between clinical groups at baseline, end of second month and end of sixth month. There were statistically significant differences between clinical and ultrasound indices and confirmed that PDS is more sensitive in detection and follow-up of clinically silent cases of JRA. PDS holds great promise for detection of active synovial inflammatory disease in sub-clinical cases of JRA and is useful in objective assessment of therapeutic response

31. STEPHENS S, SINGH-GREWAL D, BAR-OR O, BEYENE J, CAMERON B, LEBLANC CM, SCHNEIDER R, SCHNEIDERMAN-WALKER J, SELVADURAI H, SILVERMAN E, SPIEGEL L, TSE SM, WRIGHT Vet FELDMAN BM: Reliability of exercise testing and functional activity questionnaires in children with juvenile arthritis, Arthritis Rheum., Vol. 57(8), 1446-1452., 2007
    Organism:The Hospital for Sick Children, Toronto, Ontario, Canada
    Abstract:OBJECTIVE: To determine the reliability of formal exercise testing and the reliability of functional and activity questionnaires in children with juvenile idiopathic arthritis (JIA). METHODS: Children with JIA of any subtype ages 8-16 years who were recruited to a randomized trial comparing different exercise therapies participated in 2 preintervention sessions of exercise testing 2-6 weeks apart. Exercise testing included 1) submaximal oxygen uptake (VO(2submax)), 2) peak VO(2) (VO(2peak)), and 3) anaerobic power using modified Wingate tests (W(ant)). Two physical function questionnaires (the Childhood Health Assessment Questionnaire [C-HAQ] and Revised Activity Scale for Kids [ASK]) and 1 daily physical activity questionnaire (the Habitual Activity Estimation Scale [HAES]) were also completed at these times. Test-retest reliability was assessed using type 3, intrarater intraclass correlation coefficient (ICC(3,1)) and Bland and Altman plots were used to determine limits of agreement. RESULTS: Data were available for 74 patients (58 girls). VO(2submax), VO(2peak), and W(ant) demonstrated high reliability (ICC(3,1) 0.82, 0.91, and 0.94, respectively). C-HAQ and ASK questionnaires also had very high reliability (ICC(3,1) 0.82 and 0.91, respectively). The HAES demonstrated low reliability for total activity score (ICC(3,1) 0.15) and moderate reliability when the number of very active hours was analyzed separately (ICC(3,1) 0.59). CONCLUSION: Results of this investigation suggest that exercise testing and functional questionnaires in children with JIA are consistent and reliable. Reliability of the HAES total score was poor, but moderate when the very active hours subscale score was used

32. STRINGER DE, GILBERT DH, HERFORD ASet BOYNE PJ: A method of treating the patient with postpubescent juvenile rheumatoid arthritis, J.Oral Maxillofac.Surg., Vol. 65(10), 1998-2004., 2007
    Organism:Department of Oral and Maxillofacial Surgery, Loma Linda University, Loma Linda, CA, USA omfsdale@aolcomFAU - Stringer, Dale E
    Abstract:PURPOSE: Juvenile rheumatoid arthritis (JRA) is a perplexing and devastating disease for which establishment of a treatment protocol is difficult. The relatively low incidence and unknown cause of this disorder have made it difficult to establish when and how to intervene. Treatment protocols for the prepubescent patient (<12 years for girls and 14 years for boys), as well as for the adult, have been established. A protocol for postpubescence (ages 12 through 18 years) has yet to be established. This pilot study attempts to establish another treatment protocol for this particular subgroup of patients. PATIENTS AND METHODS: Five girls between the ages of 14 and 18 years with common facial deformities who were given a diagnosis of juvenile rheumatoid arthritis were reconstructed by orthognathic surgery and costochondral rib grafts. All underwent surgery performed by the first author and were followed for 4 to 14 years. Patients were in disease remission at the time of surgery, and all presented with the same skeletal/dental deformity and condylar destruction. RESULTS: Serial cephalograms were taken immediately presurgically (T1), immediately postsurgically (T2), and at latest recall (T3). Tracings were done by the same orthodontist with the use of Quick Ceph Image Pro software (Quick Ceph Systems, San Diego, CA). Mandibular position as it related to the success of costochondral and orthognathic surgery was assessed by gnathion position relative to nasion-basion at the cranial center, as described by Rickett's facial analysis. Patient long-term follow-up lasted from 4 to 14 years and had a mean duration of 9.6 years. The average increase in anterior/posterior direction (T1 to T2) was 22.7 mm with an average relapse (T2 to T3) of 1.5 mm. Four of 5 patients had a stable Class I occlusion on follow-up, and 1 developed a 3-mm open bite postoperatively. CONCLUSION: This pilot study offers a treatment protocol for the postpubescent juvenile patient with rheumatoid arthritis (aged 12 to 18 years) that is based on a single surgery with relative postoperative stability

33. TAKEUCHI T, NAKANISHI T, TABUSHI Y, HATA A, SHODA T, KOTANI T, SHIMIZU A, TAKUBO T, MAKINO Set HANAFUSA T: Serum protein profile of rheumatoid arthritis treated with anti-TNF therapy (infliximab), J.Chromatogr.B Analyt.Technol.Biomed.Life Sci., Vol. 855(1), 66-70., 2007
    Organism:First Department of Internal Medicine, Osaka Medical College, Daigaku-Machi 2-7, Takatsuki, Osaka 569-8686, Japan t-takeuchi@pohosaka-medacjpFAU - Takeuchi, Tohru
    Abstract:We analyzed the changes in the serum protein profile by infliximab using two-dimensional gel electrophoresis and mass spectrometry. More than 50 gel spots were seen to increase or decrease in correlation with clinical improvements of RA. The spots corresponding to CRP, C3, and Apo J showed reduced staining intensity, while the spots corresponding to Apo A-I, RBP, and transthyretin were enhanced. The protein profile of RA patients treated with infliximab was mostly similar to that of normal healthy controls except for several protein spots. This suggested that infliximab normalized the serum protein profile of RA patients, leading to modification in the serum lipid profile and antioxidant status in RA

34. VAN ROSSUM MA, VAN SOESBERGEN RM, BOERS M, ZWINDERMAN AH, FISELIER TJ, FRANSSEN MJ, TEN CATE R, SUIJLEKOM-SMIT LW, WULFFRAAT NM, VAN LUIJK WH, OOSTVEEN JC, KUIS Wet DIJKMANS BA: Long-term outcome of juvenile idiopathic arthritis following a placebo-controlled trial: sustained benefits of early sulfasalazine treatment, Ann.Rheum.Dis., Vol. 66(11), 1518-1524., 2007
    Organism:Emma Children's Hospital AMC, Paediatric Rheumatology, G8-205, PO Box 22660, 1100 DD Amsterdam, The Netherlands mavanrossum@amcuvanlFAU - van Rossum, Marion A J
    Abstract:OBJECTIVES: A previous 24-week randomised trial demonstrated that sulfasalazine (SSZ) treatment was superior to placebo (PLAC) in suppressing disease activity in patients with oligo- and polyarticular onset juvenile idiopathic arthritis (JIA). The current study determines the long-term outcome of the trial participants and evaluates whether the benefits of SSZ allocation are sustained over time. METHODS: Between 2001 and 2003, 32 SSZ and 29 PLAC patients (90% of all patients) were prospectively examined clinically and by chart review, median 9 years (range 7 to 10) after trial inclusion. In the follow-up assessment, variables of the American College of Rheumatology Pediatric 30 (ACR Pedi 30) criteria were collected. The assessor was blinded to trial treatment allocation. RESULTS: After the trial, patients had been routinely followed in rheumatology referral centres, and treated at the discretion of the attending physician. Almost all patients continued or started disease-modifying antirheumatic drugs (DMARDs) (SSZ 91%, PLAC 93%; SSZ treatment in about 80%). DMARD treatment appeared less intensive in the SSZ group as evidenced by a significantly shorter duration of SSZ use (median 2.5 vs 5.2 years; p = 0.02) and a trend towards less use of methotrexate and other DMARDs. More than one-third of the patients reported long periods of non-compliance with DMARD treatment in both groups. At follow-up, 74% of the patients had active joints, and 30% showed active polyarthritis. Almost all outcome scores were better for SSZ compared with PLAC patients. Differences (often exceeding 50%) were significant for the number of active joints, patients' overall well-being, number of patients with episodes of clinical remission off medication (CROM) and duration of these episodes, patients in CROM and ACR Pedi 30 response at follow-up. Additional exploratory analyses performed to detect potential confounders related to patient characteristics or follow-up treatment showed that DMARD treatment compliance was positively correlated with an ACR Pedi 30 response (odds ratio 3.8, 95% confidence interval (CI) 1.1 to 13.4; p = 0.03). Adjusted for compliance, an SSZ patient was 4.2 times as likely as a PLAC patient to be an ACR Pedi 30 responder at follow-up (95% CI 1.3 to 14.3; p = 0.02). CONCLUSIONS: This follow-up study shows that effective suppression of disease activity by SSZ treatment early in active disease in JIA patients has beneficial effects that persist for many years. Given these results, compliance with DMARD treatment deserves serious attention

35. VIKEN MK, SOLLID HD, JONER G, DAHL-JORGENSEN K, RONNINGEN KS, UNDLIEN DE, FLATO B, SELVAAG AM, FORRE O, KVIEN TK, THORSBY E, MELMS A, TOLOSA Eet LIE BA: Polymorphisms in the cathepsin L2 (CTSL2) gene show association with type 1 diabetes and early-onset myasthenia gravis, Hum.Immunol., Vol. 68(9), 748-755., 2007
    Organism:Institute of Immunology, Faculty Division Rikshospitalet, University of Oslo, Oslo, Norway mkviken@medisinuionoFAU - Viken, Marte K
    Abstract:Type 1 diabetes (T1D) is an autoimmune disease characterized by loss of beta cells in the pancreas. The CTSL2 gene encodes the cysteine protease cathepsin V involved in antigen presentation in human cortical thymic epithelial cells, and involvement of the protease in autoimmunity has been suggested. This study aimed to evaluate CTSL2 as a candidate gene for T1D, and test whether the gene predisposes more generally to autoimmune diseases. Four polymorphisms aiming at tagging the CTSL2 locus were genotyped in 421 T1D families, and subsequently in 861 rheumatoid arthritis patients, 530 juvenile idiopathic arthritis patients, and 559 controls of Norwegian origin. Additionally, DNA from 83 German myasthenia gravis (MG) patients and 244 controls were investigated. A polymorphism, rs16919034, situated downstream of CTSL2 was associated with T1D (60.8%T, p = 0.008; p(c) = 0.03). An association with early-onset MG (45% in cases vs 36.6% in controls; p = 0.03) was observed for another polymorphism (rs4361859) situated upstream of the gene, but within the same linkage disequilibrium block. No association was observed in rheumatoid arthritis or juvenile idiopathic arthritis. Our findings suggest that the CTSL2 gene is associated with T1D and with early-onset MG

36. VOJVODICH PF, HANSEN JB, ANDERSSON U, SAVENDAHL Let HAGELBERG S: Etanercept Treatment Improves Longitudinal Growth in Prepubertal Children with Juvenile Idiopathic Arthritis, J.Rheumatol., Vol. ., 2007
    Organism:From the Pediatric Endocrinology and Pediatric Rheumatology Units, Department of Woman and Child Health, Karolinska University Hospital, Stockholm, Sweden, and the Department of Epidemiology, Novo Nordisk A/S, Bagsvaerd, Denmark
    Abstract:OBJECTIVE: Anti-tumor necrosis factor (TNF) therapy is known to decrease disease activity of juvenile idiopathic arthritis (JIA), but its effect on longitudinal growth in relation to puberty is not clear. We studied longitudinal growth in response to etanercept treatment in prepubertal and pubertal patients with JIA. METHODS: Out of 52 children treated with etanercept, we studied 20 prepubertal and 11 early/midpubertal patients adherent to treatment for at least 1 year. We collected data on growth and glucocorticoid medication and calculated each patient's height standard deviation score (SDS) in relation to the mid-parental height, the change of this value (DeltahSDS) from 1 to 0 and 0 to 1 year of treatment, and the change between the DeltahSDS values to assess growth improvement. RESULTS: In the prepubertal group, the relative height SDS (mean +/- standard error of the mean) was 1.8 +/- 0.2, 2.1 +/- 0.3, and 1.9 +/- 0.3, and in the pubertal group 1.1 +/- 0.4, 1.3 +/- 0.3, and 1.1 +/- 0.3 at 1, 0, and +1 year of treatment, respectively. The DeltahSDS before etanercept was 0.3 +/- 0.1 in prepubertal and 0.2 +/- 0.2 in pubertal patients. Over the first year with etanercept, DeltahSDS was +0.2 +/- 0.1 in prepubertal (p = 0.001 vs before etanercept; paired Student t-test) and +0.2 +/- 0.1 in pubertal patients (p = 0.071). Nevertheless, most prepubertal (17/20) and pubertal (8/11) patients had improved growth (DeltahSDS) in response to etanercept treatment when analyzed individually. The need for intraarticular glucocorticoid injections was negatively correlated to the improved growth (p = 0.001). CONCLUSION: TNF inhibition with etanercept improved growth in a majority of patients with JIA. Our data demonstrate that growth improvement with etanercept was independent of the pubertal growth spurt

37. WITTKOWSKI H, HIRONO K, ICHIDA F, VOGL T, YE F, YANLIN X, SAITO K, UESE K, MIYAWAKI T, VIEMANN D, ROTH Jet FOELL D: Acute Kawasaki disease is associated with reverse regulation of soluble receptor for advance glycation end products and its proinflammatory ligand S100A12, Arthritis Rheum., Vol. 56(12), 4174-4181., 2007
    Organism:Interdisciplinary Centre for Clinical Research, University of Muenster, Muenster, Germany
    Abstract:OBJECTIVE: Receptor for advanced glycation end products (RAGE) serves as a pattern recognition receptor for several endogenous ligands that are potent inducers of inflammation. By activating endothelial cells and leukocytes, RAGE augments recruitment of leukocytes to sites of inflammation, which is a key process, especially in vasculitis. Soluble RAGE (sRAGE) acts as a naturally occurring inhibitor of RAGE by neutralizing proinflammatory ligands, e.g., S100A12. This neutrophil-derived protein has been reported to be associated with Kawasaki disease (KD) and to provoke proinflammatory responses. The aim of this study was to investigate circulating sRAGE in an acute inflammatory disorder and to compare these data directly with concentrations of the proinflammatory RAGE ligand S100A12. METHODS: Serum concentrations of sRAGE and S100A12 were analyzed by specific enzyme-linked immunosorbent assays in 50 children with KD, and additionally in 39 patients with juvenile idiopathic arthritis (JIA). In 28 of the patients with KD, levels were analyzed longitudinally over the course of the disease. RESULTS: Patients with KD and those with systemic-onset JIA had decreased levels of sRAGE during active disease, especially those patients with KD who were more severely affected and not responding to treatment. In addition, the level of sRAGE correlated negatively with the level of proinflammatory S100A12. After intravenous immunoglobulin (IVIG) therapy in patients with KD, the S100A12:sRAGE ratio was significantly different between responders and nonresponders. CONCLUSION: Inverse regulation of both sRAGE and its proinflammatory ligand S100A12 seems to be a relevant molecular mechanism promoting systemic inflammation. Calculating the S100A12:sRAGE ratio might help to detect patients with KD who are at risk of being unresponsive to IVIG therapy

38. ZEFT A, SHEAR ES, THOMPSON SD, GLASS DNet PRAHALAD S: Familial autoimmunity: maternal parent-of-origin effect in juvenile idiopathic arthritis, Clin.Rheumatol., Vol. ., 2007
    Organism:Division of Immunology and Rheumatology, Department of Pediatrics, University of Utah School of Medicine, PO Box 581289, Salt Lake City, UT, 84158-1289, USA, prahal@geneticsutahedu
    Abstract:Juvenile idiopathic arthritis (JIA) is an autoimmune (AI) disease characterized by chronic arthritis in children. Children with JIA have increased prevalence of other AI diseases. Furthermore, relatives of children with JIA have been shown to have an increased prevalence of AI diseases. Our objective was to determine if there were differences in the prevalence of AI diseases among maternal and paternal relatives of children with JIA. Information about AI diseases among all living first- and second-degree relatives was collected by structured interviews with families of 121 simplex JIA families, 23 multiplex JIA families, and 45 control families. Overall, the prevalence of AI diseases was significantly increased among maternal second-degree relatives of cases compared to that of maternal second-degree relatives of controls [14% vs. 4.3%; p < 0.001]. The prevalence of AI diseases among mothers of JIA cases was three times that of fathers [32.3% vs. 11.4%; p < 0.0001]. The prevalence of AI diseases among all maternal second-degree relatives of children with JIA was significantly higher than that of all paternal second-degree relatives [14% vs. 7.9%; p < 0.004]. Although additional paternal effects cannot be excluded, together these results demonstrate that maternal relatives of children with JIA have an increased prevalence of autoimmunity compared to paternal relatives, suggesting that there might be a maternal parent-of-origin effect in JIA

39. ZEUNER RA, EULER HHet SCHROEDER JO: High dose intravenous immunoglobulin in autoimmune rheumatic disorders, BioDrugs., Vol. 8(5), 371-386., 1997
    Organism:2nd Medical Clinic, Christian-Albrecht-University Kiel, Kiel, GermanyFAU - Zeuner, R A
    Abstract:Since the effectiveness of high dose intravenous immunoglobulin (IVIg) was first demonstrated in autoimmune thrombocytopenia, IVIg has been investigated in the treatment of various autoimmune rheumatic disorders. Controlled randomised studies have established the efficacy of IVIg in Kawasaki's syndrome, for which combined IVIg and aspirin (acetylsalicylic acid) now constitutes the standard treatment. Another controlled study has demonstrated the benefit of IVIg in dermatomyositis. IVIg treatment in juvenile rheumatoid arthritis has produced contradictory results. Uncontrolled studies and case reports on the application of IVIg in systemic lupus erythematosus, ANCA-associated vasculitides and adult rheumatoid arthritis generally describe short term positive effects. Various mechanisms are thought to underlie the effect of IVIg on autoimmune rheumatic diseases, such as: blockade of Fc receptors;immunomodulation via anti-idiotypic interactions;inhibition of complement-mediated tissue damage;modulation of cytokine expression by leucocytes and endothelial cells; andinhibition of superantigen-mediated T cell activation. IVIg is considered to be a low-risk form of treatment. Reported adverse effects include headache, aseptic meningitis and transient impairment of renal function. Haemolysis and anaphylactic reactions are rare. The effect profile of IVIg makes it a relevant, although still experimental, form of treatment in autoimmune rheumatic disorders, but its high cost renders it unsuitable as a first-line treatment. Because IVIg does not weaken patients' resistance to infection, it might serve as a therapeutic option in bridging clinical situations where immunosuppressive or cytotoxic approaches are contraindicated in patients with autoimmune disorders, such as intercurrent infection or in the period immediately before and after surgery