Bibliography October 2006

1. ALEXIS AFet STROBER BE: Off-label dermatologic uses of anti-TNF-a therapies, J.Cutan.Med.Surg., Vol. 9(6), 296-302., 2005
   Organism:Department of Dermatology, St Luke's-Roosevelt Hospital Center, New York, NY, USAFAU - Alexis, Andrew F
   Abstract:BACKGROUND: Tumor necrosis factor-alpha (TNF-a) is a proinflammatory cytokine that plays an immunomodulatory role in a variety of systemic and dermatologic diseases. Currently, three anti-TNF-a drugs are available in North America- infliximab (approved in the U.S. for the treatment of rheumatoid arthritis, Crohn's disease, ankylosing spondylitis, ulcerative colitis, and psoriatic arthritis), etanercept (approved in the U.S. for the treatment of rheumatoid arthritis, juvenile rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, and psoriasis), and adalimumab (approved for the treatment of rheumatoid arthritis and psoriatic arthritis). OBJECTIVE: To review the current literature supporting alternative (and currently off-label) dermatologic uses of TNF-a antagonists. METHODS: A MEDLINE search (1966-March 2005) was conducted using the keywords "infliximab," "etanercept," "adalimumab," "TNF inhibitors," and "off-label" to identify published reports of off-label dermatologic uses of TNF-a inhibitors. RESULTS: Anti-TNF-a therapies have been reported in the following dermatologic diseases: sarcoidosis, hidradenitis suppuritiva, cicatricial pemphigoid, Behcet's disease, pyoderma gangrenosum, multicentric reticulohistiocytosis, apthous stomatitis, Sneddon-Wilkinson disease, SAPHO syndrome, pityriasis rubra pilaris, eosinophilic fasciitis, panniculitis, Crohn's disease, necrobiosis lipoidica diabeticorum, dermatomyositis, and scleroderma. The vast majority of these reports are in the form of individual case reports and small case series. Only two published randomized controlled trials involving the off-label use of a TNF inhibitor were found. CONCLUSIONS: A growing number of published reports suggest that anti-TNF-a therapies may be effective in the treatment of numerous inflammatory skin diseases outside their currently approved indications

2. ALSAEID K, HAIDER MZ, SHARMA PNet AYOUB EM: The prevalence of human leukocyte antigen (HLA) DR/DQ/DP alleles in Kuwaiti children with oligoarticular juvenile idiopathic arthritis, Rheumatol.Int., Vol. 26(3), 224-228., 2006
   Organism:Department of Pediatrics, Faculty of Medicine, Kuwait University, PO Box 24923, Safat, 13110, Kuwait khaledalsaeid@hotmailcomFAU - Alsaeid, K
   Abstract:We have determined the prevalence of human leukocyte antigen (HLA)-DR, DQ and DP alleles in Kuwaiti children with oligoarticular juvenile idiopathic arthritis (OA-JIA) and healthy controls using the PCR-SSP (sequence specific primers) method. The analysis took into account the presence of antinuclear antibodies and chronic anterior uveitis. DRB1*03 (RR 2.20, P<0.001), DRB1*08 (RR 5.280, P<0.026), DQA1*0501 (RR 1.930, P<0.001), DQB1*0304 (RR 7.920, P<0.002), DQB1*0501 (RR 3.080, P<0.007) and DPB1*0101 (RR 8.8, P<0.001) were the main HLA alleles associated with OA-JIA in Kuwaiti Arabs in this study. DRB1*03 was detected in 71% of children with positive ANA, and in 50% of children with anterior uveitis. DQA1 alleles *0501, *0103 and *0105 (P<0.001; 0.029 and 0.024 respectively) were found to be associated with OA-JIA. In contrast, DQA1*0301 and DQA1*0302 alleles appear to be protective in Kuwaiti children (RR 0.153, P<0.001 and RR 0.278, P<0.016 respectively). The DQB1 alleles *0304 and *0501 were associated with OA-JIA (P<0.002 and P<0.007 respectively). In the case of DPB1, only one allele (*0101) was associated with OA-JIA (P<0.001). Most Kuwaiti Arab patients with OA-JIA who carried a DQ or DP susceptibility allele also had an accompanying DRB1*03 or *8 allele

3. ARCHBOLD KH, LENTZ MJ, BRANDT P, BEITZ L, WALLACE C et LANDIS CA: Sleep, pain and mood in children with juvenile rheumatoid arthritis, A88, 17-06-2001

4. ARKELA-KAUTIAINEN M, HAAPASAARI J, KAUTIAINEN H, LEPPANEN L, VILKKUMAA I, MALKIA Eet LEIRISALO-REPO M: Functioning and preferences for improvement of health among patients with juvenile idiopathic arthritis in early adulthood using the WHOICF model, Rinsho Ganka, Vol. 33, 1369-1376., 2006
   Organism:Likolahdenkatu 43, FIN-44150 Aanekoski, Finland Finland
   Abstract:Objective. To evaluate functioning and preferences for health among young adult patients with juvenile idiopathic arthritis (JIA) and controls. The WHO International Classification of Functioning. Disability and Health (ICF) was used as a framework.Methods. The patient files of a rheumatology hospital were screened to identify patients with juvenile arthritis born 1976 to 1980. Functioning was measured by the Finnish version of the Multidimensional Health Assessment Questionnaire (MDHAQ) within the framework of the ICF. Preferences in improvement of health were measured by the Finnish version of the Arthritis Impact Measurement Scales 2. Age and sex matched controls from the community were selected front the Finnish population registry.Results. In all, 123 patients with a mean age of 23 (range 21-26) years participated in the followup study. The mean time from diagnosis to followup was 16.2 years. Among them. 35% (n = 43) were in remission at followup. Lower levels of functioning for 3 ICF components were found in patients with active disease compared to controls. JIA patients with active disease had more pain and lower levels of mobility, self-care, and domestic and social life compared to controls. Patients with active disease differed from those in rem ission with pain in preferences for improvement of health.Conclusion. Patients with active disease need active treatment and rehabilitation to maintain functioning and decrease pain. The ICF offers a promising model to examine the outcomes of adult patients with JIA. Application of the MDHAQ is supported by our evaluation studies in young adults with JIA

5. BHATTACHARYA N: Placental umbilical cord whole blood transfusion to combat anemia in the background of advanced rheumatoid arthritis and emaciation and its potential role as immunoadjuvant therapy, Clin.Exp.Obstet.Gynecol., Vol. 33(1), 28-33., 2006
   Organism:Surgeon and Superintendent, Bijoygarh State Hospital, and Moore Avenue Specialist Polyclinic, Calcutta, IndiaFAU - Bhattacharya, N
   Abstract:Rheumatoid arthritis is the commonest form of inflammatory arthritis and affects about 1-3% of the population in the West and even more in the developing world due to the compounded factors of late detection and inadequate treatment in the overall background of poverty, deprivation, and improper macro and micronutrients in the diet in a sizeable segment of the population. Nearly 90% of patients with aggressive disease will become clinically disabled within 20 years. Furthermore, in patients with severe disease or extra-articular symptoms, mortality is equal to that for patients with triple artery coronary artery disease or Stage IV Hodgkin's lymphoma. Anemia is a very common comorbidity of rheumatoid arthritis. Anemia in rheumatoid arthritis is caused by various factors, for instance, cytokine impact of the advanced arthritic process on the host, or lack of proper nutrition and essential micronutrients in the diet, or coexistent helminthiasis, and/or impact of antiarthritic drugs on the host system, i.e., high steroid induced gastritis or ulcerations in gastric mucosa or subclinical or clinical hepatitis due to methotrexate or salazopyrin effects on bone marrow, only to name a few. Other pre-existing or compounding gastrointestinal problems, which alter the available iron stores or cause bone marrow dysfunction, may also help in adding to an anemic condition. If the anemia is 8 g/dl or less, blood transfusion or erythropoietin injection with adequate hematinic reserve is effective in normal situations, but is not that effective in anemia with a chronic disease background like rheumatoid arthritis. Cord blood, because of its rich mix of fetal and adult hemoglobin, high platelet and white blood cell (WBC) counts, and a plasma filled with cytokine and growth factors, as well as its hypo antigenic nature and altered metabolic profile, has all the potential of a real and safe alternative to adult blood transfusion. Seventy-eight units (42 ml -136 ml mean 80.6 ml +/- 3.6 ml SD, median 82.4 ml, mean packed cell volume 48.2 +/- 2.1 SD, mean percent hemoglobin concentration 16.4 g/dl +/- 1.5 g/dl SD) of placental umbilical cord whole blood was transfused (from 1 April 1999 to April 2005) after lower uterine cesarean section (LUCS) from consenting mothers to 28 informed consenting patients with advanced rheumatoid arthritis who had plasma hemoglobin of 8 g/dl or less. After collection, the blood was immediately transfused following the standard adult blood transfusion protocol. Each case was passed through the institutional ethical committee. The patients received two to six units of freshly collected placental umbilical cord blood without encountering any clinical, immunological or non-immunological reactions. Three days after completion of the transfusion of placental umbilical cord blood, the peripheral blood hematopoietic stem cell (CD34) estimation revealed a rise from the pretransfusion base level (.09%), varying from 2.03 to 23%, which returned to base level in most of the cases at the three-month CD34 re-estimation, without provoking any clinical graft vs host reaction in any of the patients

6. BIESTER S, DEUTER C, MICHELS H, HAEFNER R, KUEMMERLE-DESCHNER J, DOYCHEVA Det ZIERHUT M: Adalimumab in the Therapy of Uveitis in Childhood, Br.J.Ophthalmol., Vol. ., 2006
   Organism:University of Tuebingen, Germany
   Abstract:PURPOSE: Chronic anterior uveitis in children often takes a serious course. Despite various immunosuppressive drugs some children do not sufficiently respond with a high risk of becoming seriously disabled. Anti-TNF alpha therapy has been shown by our group and others to be mostly ineffective (Etanercept) or partly effective (Infliximab) with the risk of anaphylactic reactions. Here we report on 18 young patients treated with Adalimumab (Humira(R)), a complete humanized anti-TNF alpha antibody. METHODS: We retrospectively analysed 18 patients, who were treated with Adalimumab (20-40 mg, every 2 weeks, when ineffective every week); 17 had juvenile idiopathic arthritis, 1 was without detectable underlying disease. The age at onset of arthritis varied from 0.5-15 years and for uveitis from 2-19 years. Patients were included when the previous anti- inflammatory therapy had been ineffective. It consisted of systemic steroids (n=18), Cyclosporin A (n=18), Methotrexate (n=18), Azathioprine (n=12), Mycophenolate mofetil (n=4), Cyclophosphamide (n=2), Leflunomide (n=3), Etanercept (n=8) and Infliximab (n=5). The grading for uveitis was: effective: no relapse or more than 2 relapses less than before treatment, mild: one relapse less than before treatment, no response: no change in relapse rate, worsening: more relapses under treatment than before. The grading for arthritis (depending on the clinical findings, using 3 out of 6 parameters of the ACR PED Criteria) was: effective, mild, no response, worsening. RESULTS: For arthritis (n=16) the response to Adalimumab was effective in 10 of 16 patients, mild in 3 patients, 3 did not respond. For uveitis (n=18) Adalimumab was effective in 16, mild in 1 child, and 1 patient did not show any effect. After a very good response initially a shorter application time had to be used to maintain the good anti-inflammatory effect in 1 child. Additional immunosuppressive treatment was used in 7 of the effectively treated children. Due to elevation of liver enzymes in 1 patient, who also took MTX, Adalimumab had to be discontinued. No anaphylactic reactions or increased frequency of infections since start of Adalimumab treatment was reported. CONCLUSIONS: For our group of children with long lasting disease our results show that Adalimumab was effective or mildly effective against the arthritis in 81%, but in uveitis in 88%. While these results regarding arthritis are comparable with other TNF-alpha blocking drugs (Etanercept), Adalimumab seems to be much more effective against uveitis than Etanercept. Anaphylactic reactions, found in a previous study from our group after Infliximab treatment, are not seen with Adalimumab. The necessary dosage and the treatment period, which probably have to be defined individually for each patient, remain unclear

7. BRUNNER HI, KIM KN, BALLINGER SH, BOWYER SL, GRIFFIN TA, HIGGINS GC, MIER R, PASSO MH, RENNEBOHM R, SCHIKLER Ket LOVELL DJ: Current Medication Choices in Juvenile Rheumatoid Arthritis II -Update of a Survey Performed in 1993, J.Clin.Rheumatol., Vol. 7(5), 295-300., 2001
   Organism:Children's Hospital Medical Center Cincinnati, Ohio (HB, KK, TG, MP, DL) James Whitcomb Riley Hospital Indianapolis, Indiana, (SHB, SLB) Children's Hospital, Columbus Ohio (GH, RR) Shriner's Hospital Lexington, Kentucky (RM) Department of Pediatrics University of Louisville, Louisville Kentucky (KS)
   Abstract:The documentation of treatments used for Juvenile Rheumatoid Arthritis (JRA) is important to allow for the evaluation of practice patterns for future outcome studies. A survey of nine pediatric rheumatologists was performed between September 1999 and February 2000. Each of the physicians prospectively recorded demographic and treatment information on consecutively sampled JRA patients (n=395). Pauciarticular onset JRA was present in 46%, polyarticular onset JRA in 35%, and systemic onset JRA in 19% of the children. Naproxen was the most frequently prescribed medication (55% of the patients), followed by methotrexate (MTX), which was used in 39% of the patients. Folic acid supplementation (1 mg/day) was provided to 69% of the patients treated with MTX. Etanercept was used in 11% of the children. Eleven percent of the patients received corticosteroids, and 13% of children on corticosteroids took calcium supplements. Uveitis was present in 8% and had a chronic course in 79% of those cases. Although systemic medications were used in 50% of the children with uveitis to control eye inflammation, severe damage to the eyes developed in 30% of them. Fourteen percent of the patients required gastroprotective medications. Compared with findings of a similar survey performed in 1993, there was no significant change in the frequency of use of naproxen, but nabumetone is now more often prescribed, and COX-2 inhibitors have been introduced in the therapy of JRA. Changes among second-line agents used for JRA have also occurred, although there was no change in the frequency of use of MTX or corticosteroids. JRA continues to be a treatment challenge for the practicing pediatric rheumatologist. Patients often show incomplete response to the currently available medications. Therefore, new therapeutic agents need to be evaluated for their use in JRA, and the treatment of JRA associated uveitis especially needs to be improved

8. CORNILLET A, CAMUS C, NIMUBONA S, GANDEMER V, TATTEVIN P, BELLEGUIC C, CHEVRIER S, MEUNIER C, LEBERT C, AUPEE M, CAULET-MAUGENDRE S, FAUCHEUX M, LELONG B, LERAY E, GUIGUEN Cet GANGNEUX JP: Comparison of epidemiological, clinical, and biological features of invasive aspergillosis in neutropenic and nonneutropenic patients: a 6-year survey, Clin.Infect.Dis., Vol. 43(5), 577-584., 2006
   Organism:Laboratoire de Parasitologie-Mycologie,Hopital Pontchaillou, Rennes, FranceFAU - Cornillet, A
   Abstract:BACKGROUND: Invasive aspergillosis is an opportunistic infection that occurs mainly among patients with prolonged neutropenia. Few data are available on invasive aspergillosis in nonneutropenic patients. METHODS: The aim of this survey was to compare neutropenic and nonneutropenic patients who had received a diagnosis of invasive aspergillosis at our institution during a 6-year period. RESULTS: Among the 88 cases of invasive aspergillosis analyzed here, 12 were histologically proven, 52 were probable, and 24 were possible. Forty-seven percent of cases were diagnosed in the intensive care unit, and 40% were diagnosed in hematology units. Neutropenia was a risk factor for 52 patients (59%), most of whom had hematological or solid malignancies. Among the 36 nonneutropenic patients (41%), the main underlying conditions were steroid-treated chronic obstructive pulmonary disease, asthma, rheumatoid arthritis, giant-cell arteritis, and microvascular disorders; 10 patients were recipients of solid-organ transplants, and 1 patient was seropositive for human immunodeficiency virus. The distribution of proven and probable invasive aspergillosis was similar for neutropenic and nonneutropenic patients. The mortality rate was 71.5% overall and was significantly higher among nonneutropenic patients than among neutropenic patients (89% vs. 60%; P<.05). Compared with neutropenic patients, nonneutropenic patients were significantly less likely to have symptoms of invasive aspergillosis and more likely to have frequent intercurrent pneumonia due to another microorganism. The sensitivity of mycological examination of bronchoalveolar lavage fluid specimens was higher for nonneutropenic patients than for neutropenic patients (85% vs. 58%; P<.05), whereas the sensitivity of antigenemia was the same for the 2 populations (65% vs. 64%). Findings on thoracic computed tomographs were similar, except that segmental areas of consolidation occurred more frequently among neutropenic patients. CONCLUSION: This survey at a whole institution underlines the high number of cases of invasive aspergillosis among nonneutropenic patients, with an overall mortality rate that was significantly higher than that for neutropenic patients

9. DANNER S, SORDET C, TERZIC J, DONATO L, VELTEN M, FISCHBACH Met SIBILIA J: Epidemiology of juvenile idiopathic arthritis in Alsace, France, Rinsho Ganka, Vol. 33, 1377-1381., 2006
   Organism:CHU Hautepierre, Dept Rheumatol, F-67098 Strasbourg, France France
   Abstract:Objective. To determine the incidence, prevalence. and principal characteristics of the different forms of juvenile idiopathic arthritis (JIA) in the region of Alsace, northeastern France. using the new classification of the International League of Associations for Rheumatology (ILAR).Methods. In 2002 we performed a retrospective epidemiologic study pertaining to the year 2001. The pediatricians, rheumatologists, ophthalmologists. orthopedic surgeons. and physicians involved in functional reeducation in the Alsace region were interviewed. and all patients were classified according to the new I LAR classification using the criteria revised in Durban in 1997.Results. Among the 361 clinicians contacted. the participation rate was 97.8%. The study identified 67 children followed for JIA in Alsace in 2001, from a total population of 1.8 million inhabitants including 339,095 children under age 16 years. The incidence was calculated to be 3.2 cases/100,000/year and the prevalence 19.8 cases/100,000 children under age 16 years. Among these 67 cases of JIA. the most frequent forms were oligoarthritis (n = 27, 40.3%), polyarthritis without rheumatoid factor (RF: n = 15 22.4%), and enthesitis related arthritis (n = 12, 17.9%). Other forms, notably systemic arthritis (n = 6, 8.9%) and psoriatic arthritis (n = 3, 4.5%), were more rare and in this study there was no case of polyarthritis with RE Only 4 patients (6%) were classified in the undifferentiated arthritis group using the new classification. Antinuclear antibodies (ANA: by indirect immunofluorescence. HEp > 1/80) were detected in patients with oligoarthritis (81%) and polyarthritis without RF (79%). Uveitis occurred in 41% of children with oligoarthritis and in 14% of those with polvarthritis without RF.Conclusion. Our results are comparable to those of other studies carried out in Caucasian populations with regard to incidence and prevalence. This work also highlights the frequent presence of ANA and uveitis in patients with oligoarthritis or polyarthritis without RF

10. EHLERT K, GROLL AH, KUEHN Jet VORMOOR J: Treatment of refractory CMV-infection following hematopoietic stem cell transplantation with the combination of foscarnet and leflunomide, Klin.Padiatr., Vol. 218(3), 180-184., 2006
    Organism:University Hospital Muenster, Department of Pediatric Hematology and Oncology, Muenster ehlertk@mednetuni-muensterdeFAU - Ehlert, K
    Abstract:BACKGROUND: Treatment of cytomegalovirus (CMV) disease after allogeneic hematopoietic stem cell transplantation (HSCT) is limited by toxicities of current antiviral drugs and the occurrence of drug resistant strains. Leflunomide, an immunosuppressive agent used for treatment of rheumatoid arthritis, also has activity against CMV by impairing viral assembly. Here we report the control of refractory CMV disease by the combined use of foscarnet and leflunomide. PATIENTS AND RESULTS: A 1S-year-old boy with juvenile myelo-monocytic leukemia (JMML) received an allogeneic HSCT with bone marrow stem cells from a mismatched, unrelated donor (MMUD, recipient and donor CMV-positive). CMV-reactivation two months post transplantation (Tx) could only be controlled by the use of cidofovir. Because of secondary graft failure, the boy received a second HSCT with peripheral blood stem cells (PBSC) of the same donor after overall 6 months. CMV-infection was noticed three weeks later, associated with a considerable rise of both CMV-copy number and pp65-antigen. Since reinduction with cidofovir was ineffective and ganciclovir not warranted due to the history of graft failure, the child then received a combination of foscarnet/leflunomide, leading to a rapid decline of his CMV-copy number and to an afebrile state. Hematological, hepatic or renal toxicities were not observed. CONCLUSION: This case report suggests that leflunomide may be of use in the management of transplant recipients with CMV-infection refractory or intolerant to conventional antiviral therapy

11. ESHED I, ALTHOFF CE, SCHINK T, SCHEEL AK, SCHIRMER C, BACKHAUS M, LEMBCKE A, BOLLOW M, HAMM Bet HERMANN KG: Low-field MRI for assessing synovitis in patients with rheumatoid arthritis. Impact of Gd-DTPA dose on synovitis scoring, Scand.J.Rheumatol., Vol. 35(4), 277-282., 2006
    Organism:Department of Radiology, Charite Medical School, Campus Mitte, Schumannstrasse 20-21, 10117 Berlin, GermanyFAU - Eshed, I
    Abstract:OBJECTIVE: To investigate the impact of a double dose compared to a single dose of contrast material in low-field magnetic resonance imaging (MRI) on semi-quantitative scoring of synovitis in patients with rheumatoid arthritis (RA). METHODS: This prospective study included 38 RA patients (23 women and 15 men, mean age 51 years). All patients underwent low-field MRI of the hand before administration of contrast medium, after intravenous injection of 0.1 mmol/kg gadolinium diethylenetriaminepentaacetic acid (Gd-DTPA), and after another dose of 0.1 mmol/kg Gd-DTPA. Two readers (A and B) blinded to dosage independently scored the single dose and double dose image sets for synovitis according to outcome measures in rheumatology (OMERACT) recommendations. Contrast-to-noise ratio (CNR) and signal-to-noise ratio (SNR) were also calculated for each set. RESULTS: 149 metacarpophalangeal (MCP) joints were evaluated. There was good inter-reader agreement for each of the two sets (intra-class correlation coefficient of 0.75 for the single dose set and 0.83 for the double dose). Median CNR and SNR values were 5.4 and 15.9, respectively, for the single dose set and 8.5 and 16.6, respectively, for the double dose set (p<0.0001). Single dose set mean synovitis scores were 1.7 and 1.6 for readers A and B, respectively. Double dose set scores were 1.9 and 2.0, respectively. Thus, higher synovitis scores were recorded for the double dose sets than the single dose sets (p<0.005). CONCLUSION: In low-field MRI, when evaluating RA, the dose of the contrast material influences synovitis scoring. Therefore, dosage of contrast material should be taken into consideration when using extremity dedicated low-field MRI

12. FLATO B, HOFFMANN-VOLD AM, REIFF A, FORRE O, LIEN Get VINJE O: Long-term outcome and prognostic factors in enthesitis-related arthritis: A case-control study, Arthritis Rheum., Vol. 54(11), 3573-3582., 2006
    Organism:Rikshospitalet-Radiumhospitalet Medical Center, Oslo, Norway
    Abstract:OBJECTIVE: To compare the clinical, functional, and radiographic outcomes in patients with enthesitis-related arthritis (ERA) with those in patients with other subtypes of juvenile idiopathic arthritis (JIA) and healthy controls, and to determine genetic markers, patient characteristics, and early disease variables that predict the development of remission, sacroiliitis, and physical limitations in ERA. METHODS: Fifty-five children with ERA who were first admitted to Rikshospitalet Medical Center between 1980 and 1985 were studied. Patients with oligoarthritis or polyarthritis who were admitted during the same period (n = 55) and individuals from a national population registry (n = 55) were matched for sex and age and used as controls. Health status was assessed after a median of 15.3 years of disease (range 11.7-21.9 years) and, in some patients, was reassessed after a median of 23.0 years (range 19.7-29.4 years) of disease, by use of the 36-item Short Form health survey and the Health Assessment Questionnaire. Clinical and radiographic examinations were performed at the 15-year followup visit. Variables relating to the onset of disease were retrospectively obtained by chart review. HLA alleles were determined by genotyping and serologic testing. RESULTS: Patients with ERA had lower levels of physical functioning, poorer physical health, and more bodily pain compared with patients with oligoarthritis or polyarthritis (after a median of 15.3 and a median of 23.0 years) and normal controls (after a median of 15.3 years). Among patients with ERA, remission occurred in 44%, sacroiliitis was observed in 35%, and reduced spinal flexion was observed in 75%. Predictors of failure to attain disease remission included the following: ankylosing spondylitis (AS) in a first-degree relative, the presence of HLA-DRB1*08, and ankle arthritis within the first 6 months. HLA-DPB1*02 was a protective factor, whereas a persistently elevated erythrocyte sedimentation rate (ESR), and hip arthritis within the first 6 months were risk factors for sacroiliitis. Female sex, a family history of AS, and high numbers of affected joints within the first 6 months predicted poor physical health status after 23 years. Male sex was associated with reduced anterior flexion of the spine. CONCLUSION: In this study, patients with ERA had poorer physical outcomes compared with patients with oligoarticular or polyarticular JIA and controls from the general population. A family history of related diseases, sex, the presence of HLA-DRB1*08, the absence of HLA-DPB1*02, a persistently elevated ESR, early hip or ankle arthritis, and high numbers of affected joints were predictors of an unfavorable outcome

13. FOSTER HE, KAY LJ, FRISWELL M, COADY Det MYERS A: Musculoskeletal screening examination (pGALS) for school-age children based on the adult GALS screen, Arthritis Rheum., Vol. 55(5), 709-716., 2006
    Organism:The Medical School, University of Newcastle upon Tyne, Newcastle, UK hefoster@nclacukFAU - Foster, H E
    Abstract:OBJECTIVE: To develop and validate a musculoskeletal screening examination applicable to school-age children based on the adult Gait, Arms, Legs, Spine (GALS) screen. METHODS: Adult GALS was tested in consecutive school-age children attending pediatric rheumatology clinics and was compared with an examination conducted, on the same day, by a pediatric rheumatologist who classified children as having abnormal or normal joints. Adult GALS was tested for validity compared with the pediatric rheumatologist's assessment and deficiencies in adult GALS were identified. Experts proposed amendments to adult GALS, achieving consensus by modified Delphi techniques. The resultant pediatric screening tool (pGALS) was tested (methodology identical to the testing of adult GALS) in an additional group of children. RESULTS: Adult GALS was tested in 50 children (median age 11 years, range 4-16), of whom 37 (74%) had juvenile idiopathic arthritis. Adult GALS missed important abnormalities in 18% of children, mostly at the ankle, foot, and temporomandibular joints. The pGALS was tested in 65 children (median age 13 years, range 5-17 years) and demonstrated excellent sensitivity (97-100%) and specificity (98-100%) at all joints, with high acceptability scored by child and parent/guardian. The median time to perform pGALS was 2 minutes (range 1.5-3 minutes). CONCLUSION: The pGALS musculoskeletal screening tool has excellent validity, is quick to perform, and is acceptable to school-age children and parents/guardians. We propose that pGALS be incorporated into undergraduate and postgraduate medical training to improve pediatric musculoskeletal clinical skills and facilitate diagnosis and referral to specialists

14. FRAISSE TC, DEGRAEVE F, RIVIERE Set LE QUELLEC A: [Evolution and prognosis of adult onset Still's disease. A monocentric study of 17 patients], Rev.Med.Interne., Vol. 27(9), 658-664., 2006
    Organism:Service de Medecine Interne A, Hopital Saint-Eloi, 80, Avenue Augustin-Fliche, 34295 Montpellier Cedex 05, FranceFAU - Fraisse, T-C
    Abstract:Adult-Onset Still's disease (AOSD) is a rare condition of unknown origin with various presentations and unpredictable outcome. The aim of this study was to analyse clinical and biological presentation, and outcome of patients admitted to an internal medicine service. METHOD: A retrospective cohort design with prospective follow-up was used. All the patients admitted to our internal medicine service for AOSD between January 1998 and March 2004 were included. RESULTS: According to Yamaguchi's classification criteria, 17 patients were analysed with a mean age at onset of 37.3 years and a 2.4 sex-ratio (female/male). Mean follow-up length was 52.1 months. Eight patients developed a monocyclic systemic form, 8 a polycyclic systemic form and 1 a chronic articular form. Arthralgia (87%) and arthritis (53%) were less frequent than in other series. Sixteen patients were treated: 14 by corticosteroids, 6 by non-steroid anti-inflammatory drugs, 5 by methotrexate, 2 intravenous polyglobulin and one by anti-TNF drug. Patients with a corticodependant or corticoresistant form had more polyarthritis at the onset of the disease (3/6 vs 0/11, P=0.029). DISCUSSION: In internal medicine activity, AOSD without oligo- or polyarthritis may be more frequent than expected according to the literature. Corticotherapy alone is often efficient in these AOSD form without synovitis, and methotrexate use is uncommon

15. GIBSON DS, BLELOCK S, BROCKBANK S, CURRY J, HEALY A, MCALLISTER Cet ROONEY ME: Proteomic analysis of recurrent joint inflammation in juvenile idiopathic arthritis, Journal of Proteome Research, Vol. 5, 1988-1995., 2006
    Organism:Queens Univ Belfast, Arthritis Res Grp, Musculoskeletal Educ and Res Unit, Musgrave Pk Hosp, Stockmans Lane, Belfast BT9 7BL, Antrim, UK UK
    Abstract:The synovial fluid proteome in juvenile idiopathic arthritis was investigated to isolate joint-specific biomarkers that are expressed in patients displaying recurrent joint inflammation. To identify the synovial specific proteome, matched synovial fluid and plasma samples were subjected to protein separation by 2-dimension electrophoresis (2DE). Forty-three protein spots, overexpressed in the joint, were identified. Synovial fluids from children with single-event knee joint inflammation were then compared with a group with recurrent knee disease. Nine synovial specific proteins were significantly differentially expressed in the recurrent group. Proteolytic fragments of collagen X, fibrin beta-chain, and T-cell receptor alpha-region have been identified among this protein cluster. Putative biomarkers, overexpressed in the joint and differentially expressed in children with recurrent joint inflammation, have been identified. These proteins may play a significant role determining the pathological state within the chronically inflamed joint and influence disease progression in JIA. This is the first study of the synovial proteome in children

16. GOWING ECet MCKOWN KM: Myasthenia gravis in a patient with pauciarticular juvenile chronic arthritis, J.Clin.Rheumatol., Vol. 8(5), 269-272., 2002
    Organism:Section of Rheumatology, University of Wisconsin Hospital and Clinics, Madison, Wisconsin, USAFAU - Gowing, Eric C
    Abstract:There have been reported cases of children with histories of pauciarticular juvenile chronic arthritis (JCA) later developing myasthenia gravis (MG) as young adults. This is intriguing because it had been considered rare to diagnose a second autoimmune disease in a patient with pauciarticular JCA, unlike in those with adult-onset rheumatoid arthritis. We report a case of MG in a 20-year-old woman with a history of pauciarticular JCA. She presented with bilateral ptosis, weakness, and a history of dysphagia. The diagnosis was confirmed with positive serum acetylcholine receptor antibodies (2000 nm/L) and electromyography showing a decremental response to repetitive muscle stimulation. The patient's inflammatory arthritis was quiescent at diagnosis. The patient underwent a surgical thymectomy and was treated with pyridostigmine, intravenous immunoglobulin, and corticosteroids with a fluctuating clinical course. Previous cases have been reported of MG associated with this subtype of JCA, suggesting a connection in autoimmune pathology. The earlier recognition and management of MG in a patient with pauciarticular JCA presenting with weakness may improve the prognosis of this disease

17. HAMEED Ret ZACHARIN MR: Cushing syndrome, adrenal suppression and local corticosteroid use, J.Paediatr.Child Health., Vol. 42(6), 392-394., 2006
    Organism:Department of Endocrinology and Diabetes, Royal Children's Hospital, Melbourne, Victoria, AustraliaFAU - Hameed, Rubina
    Abstract:Adrenal suppression can occur following use of intra-articular corticosteroid injection for treatment of arthritis. If unrecognised, this can result in major medical illness, shock or death. We report two children who developed Cushingoid features and severe adrenal suppression after joint injection. Paediatricians caring for children who have intra-articular corticosteroid injections should be aware of this potential complication. Monitoring of cortisol levels after injection should be considered

18. HARTGRING SA, BIJLSMA JW, LAFEBER FPet VAN ROON JA: Interleukin-7 induced immunopathology in arthritis, Ann.Rheum.Dis., Vol. 65 Suppl 3, iii69-iii74, 2006
    Organism:Rheumatology and Clinical Immunology (F02127), University Medical Center Utrecht, PO Box 85500, 3508 GA Utrecht, the Netherlands JvanRoon@umcutrechtnlFAU - Hartgring, S A Y
    Abstract:Interleukin (IL)-7 is a potent immunoregulatory cytokine that is detected in joints of patients with rheumatoid and juvenile idiopathic arthritis and which correlates with parameters of disease. Several synovial cell types that play an important role in inflammation and immunopathology, such as macrophages, dendritic cells, and fibroblasts, produce IL-7. IL-7 induces cytokines produced by arthritogenic T cells (for example, interferon gamma (IFNgamma), IL-17), T cell differentiating factors (for example, IL-12), chemokines capable of attracting inflammatory cells (for example, macrophage induced gene (MIG), macrophage inflammatory protein (MIP)-1alpha) as well as molecules involved in cell adhesion, migration, and costimulation (for example, lymphocyte function associated antigen (LFA)-1, CD40, CD80). In addition, IL-7 can induce bone loss by stimulating osteoclastogenesis that is dependent on receptor activator of nuclear factor kappaB ligand (RANKL). IL-7 induces tumour necrosis factor alpha (TNFalpha) secretion by T cells and by monocytes after T cell dependent monocyte/macrophage activation. Importantly, induction of both IL-7 and IL-7 induced effects seems to be able to operate independent of TNFalpha. Together this suggests that IL-7 is an important cytokine in several rheumatic conditions, capable of inducing inflammation and immunopathology. Thus it may be an important target for immunotherapy

19. HEILIGENHAUS A: When Should Intraocular Lenses Be Implanted in Patients with Juvenile Idiopathic Arthritis-Associated Iridocyclitis?, Ophthalmic Res., Vol. %20;38(6), 316-317., 2006
    Organism:

20. HOGBERG E, STALMAN A, WREDMARK T, TSAI JA, ARNER Pet FELLANDER-TSAI L: Opioid requirement after arthroscopy is associated with decreasing glucose levels and increasing PGE2 levels in the synovial membrane, Acta Orthop., Vol. 77(4), 657-661., 2006
    Organism:Division of Orthopedics, Department of Clinical Science Intervention and Technology (CLINTEC), Karolinska University Hospital Huddinge, SE-141 86 SwedenFAU - Hogberg, Erland
    Abstract:BACKGROUND: Increased prostaglandin E2 (PGE2) release has been suggested to contribute to the enhanced nociceptor sensitivity that underlies chronic osteoarthritis pain. We have previously shown increased levels of lactate and glycerol in synovium postoperatively. Thus, we wanted to investigate whether the local trauma response is related to subjective pain. METHODS: We monitored metabolic and inflammatory changes with microdialysis in the knee joint synovial membrane of 14 patients after arthroscopy, in relation to pain requiring systemic opioids. The adipose tissue of the contralateral thigh served as reference. The concentrations of glucose, lactate, pyruvate, glycerol and PGE2, and also local blood flow were analyzed over 3 hours postoperatively. RESULTS: In the 6 patients requiring systemic opioid analgesia, the initial concentrations of glucose and PGE2 in the synovial tissue were increased compared to those not requiring opioids, and decreased following opioid administration. In the reference tissue there was no difference between groups regarding glucose, and the PGE2 concentration was below the detection limit. No significant differences in the levels of other compounds, in relation to the need for opioids, were found, either in synovial tissue or in reference tissue. Overall, the synovial tissue blood flow was stable. INTERPRETATION: Pain after arthroscopy is reflected by increased glucose utilization and PGE2 production by the synovial membrane

21. JAROS cet PUDLAC c: Affection of temporomandibular joint in rheumatic diseases|, 2006
    Organism:Clinical manifestations of temporomandibular joint (TMJ) affection in rheumatic diseases are represented by pain, restricted motion, and crepitus. We can often find advanced changes on radiography or on magnetic resonance images in patients who have no clinical manifestations. TMJ involvement was demonstrated in 17% of patients with osteoarthritis older than 76 years. In patients with rheumatoid arthritis and ankylosing spondylitis, 17-66 % and approximately one third of the patients had radiographic changes, respectively. Serious changes of mandible were found in patients with juvenile idiopathic arthritis. Magnetic resonance imaging with gadolinium enhancement show ed the benefit for the diagnosis of early TMJ changes

22. JYLLI L, BROSTROM E, HAGELBERG S, STENSTROM CH, OLSSON GLet LANGIUS-EKLOF A: Sensory and affective components of pain as recorded with the Pain-O-Meter (POM) among children with acute and chronic pain, Acta Paediatr., Vol. 95(11), 1429-1434., 2006
    Organism:Department of Women and Child Health, Pain Treatment Service, Astrid Lindgren Children's Hospital, Karolinska University Hospital, Karolinska Institute, Stockholm, SwedenFAU - Jylli, Leena
    Abstract:Aim: To explore the usefulness of the Pain-O-Meter sensory and affective words scale (POM-WDS) with regard to whether children aged 6-16 who suffer from chronic and acute pain know the words and what words they chose to describe their pain. Methods: Sixty-one children participated, mean age 11 y, suffering from acute pain (n=25) and pain associated with juvenile idiopathic arthritis (JIA, n=36). Children rated their pain intensity on the POM-VAS (visual analogue scale, 0-10 cm). Thereafter, children were asked whether each sensory and affective word on the POM-WDS was known to them, and whether each word described their pain experience. Results: Seventeen out of 23 words were known to at least 70% of the sample. The least recognized word was grinding. Children age 6-16 knew fewer words than the adolescents. Age was a significant determinant for whether the children knew the words grinding (odds ratio (OR) 20.08, p<0.01), gnawing (OR 5.92, p < 0.05), unbearable (OR 8.02, p<0.05), and excruciating (OR 20.17, p<0.001). Terrible (OR 33.3, p<0.05), aching (OR 44.5, p<0.05) and sore (OR 5.4, p<0.05) were selected more often by children with acute pain than with JIA.Conclusion: Further studies will be required to determine the suitability of using the POM-WDS with children

23. KANEIDER NC, LEGER AJet KULIOPULOS A: Therapeutic targeting of molecules involved in leukocyte-endothelial cell interactions, FEBS Journal, Vol. 273, 4416-4424., 2006
    Organism:Tufts NEMC, Mol Oncol Res Inst, 750 Washington St,Box 7510, Boston, MA 02111 USA USA
    Abstract:Inflammation is traditionally viewed as a physiological reaction to tissue injury. Leukocytes contribute to the inflammatory response by the secretion of cytotoxic and pro-inflammatory compounds, by phagocytotic activity and by targeted attack of foreign antigens. Leukocyte accumulation in tissues is important for the initial response to injury. However, the overzealous accumulation of leukocytes in tissues also contributes to a wide variety of diseases, such as atherosclerosis, chronic inflammatory bowel disease, rheum atoid arthritis, multiple sclerosis, vasculitis, systemic inflammatory response syndrome, juvenile diabetes and psoriasis. Many therapeutic interventions target immune cells after they have already migrated to the site of inflammation. This review addresses different therapeutic strategies, used to reduce or prevent leukocyte-endothelial cell interactions and communication, in order to limit the progression of inflammatory diseases

24. KOTANIEMI Ket PENTTILA H: Intraocular Lens Implantation in Patients with Juvenile Idiopathic Arthritis-Associated Uveitis, Ophthalmic Res., Vol. 38(6), 318-323., 2006
    Organism:Rheumatism Foundation Hospital, Heinola, Finland
    Abstract:Objective: To evaluate the development of cataract and the results of cataract surgery with intraocular lens (IOL) implantation in patients with chronic uveitis associated with juvenile idiopathic arthritis (JIA). Patients and Methods: A hospital-based retrospective case series consisted of 25 patients with JIA-associated uveitis. The mean age of the patients was 5.8 years at the onset of arthritis and 6.8 years at the onset of uveitis. During the 15-year study period cataract surgery with implantation of an IOL was performed in 36 eyes. In 17 eyes phacoemulsification and initial posterior capsulectomy with anterior core vitrectomy were performed. The treatment of JIA and uveitis was carefully adjusted with systemic immunosuppressive drugs and topical corticosteroids perioperatively. The mean postoperative follow-up period was 3.3 years. Results: The first signs of cataract were observed 2.3 years (mean) after the diagnosis of uveitis and the cataract operation of the first eye was performed 4.5 years (mean) after the diagnosis of uveitis. After IOL surgery the visual result was good (>/=0.5) in 64%, moderate (0.3 to <0.5) in 11% and impaired (<0.3) in 25% of eyes. Secondary cataract developed in 16 eyes but in none of the eyes with initial posterior capsulectomy and core vitrectomy. Secondary glaucoma developed in 18 eyes, retinal detachment in 2, cystoid macular edema in 16 and band keratopathy in 12 eyes. Conclusion: Cataract is an early complication of JIA-associated uveitis. Under strict control of uveitis, IOL implantation is an important alternative in visual rehabilitation for this type of patient. Copyright (c) 2006 S. Karger AG, Basel

25. KOTEVOGLU-SENERDEM N, TOYGAR Bet TOYGAR B: Thiemann Disease, J.Clin.Rheumatol., Vol. 9(6), 359-361., 2003
    Organism:From the *Sisli Etfal Teaching Hospital, Physical Therapy and Rehabilitation Department, Istanbul, Turkey; and daggerKizilay Altintepe, Physical Therapy and Rehabilitation Department, Istanbul, Turkey
    Abstract:Thiemann disease is a rare genetic disorder that is considered to be a form of avascular necrosis of the proximal interphalangeal joints of the fingers and toes. The clinical symptoms usually appear in adolescence or puberty and may be confused with juvenile rheumatoid arthritis. The characteristic symmetrical, firm, relatively painless deformity and x-ray findings of the epiphysical irregularities should suggest the diagnosis. As rheumatologists become more familiar with the disease, it may be more frequently and promptly diagnosed

26. KRENN V, MORAWIETZ L, KONIG B, OTTO M, KRIEGSMANN J, KOPENIK A, BOHME Tet HAUPL T: [Low-grade-/high-grade-synovitis: synovitis-score as a gold standard?], Orthopade., Vol. 35(8), 853-859., 2006
    Organism:Institut fur Pathologie, Moltkestrasse 32, 54292 Trier krenn@patho-trierdeFAU - Krenn, V
    Abstract:BACKGROUND: Synovectomy specimens represent important material submitted from the orthopedist to the pathologist. However, no consistent histopathological grading system for chronic synovitis has been established so far. PATIENTS AND METHODS: The three compartments of chronic synovitis (enlargement of lining cell layer, density of synovial stroma cells, leukocytic infiltrate) are graded semiquantitatively (from 0=absent to 3=strong), and the points for each compartment add up to the synovitis score: 0-1 = no synovitis, 2-4 = low-grade synovitis, 5-9 = high-grade synovitis. A total of 618 synovial specimens (resections n=559, biopsies n=59) from degenerative and inflammatory joint diseases were graded by two independent observers. RESULTS: Median synovitis scores when correlated to clinical diagnoses were: 1, control; 2, osteoarthritis and post-traumatic arthritis; 3, psoriatic arthritis; 5, reactive and rheumatoid arthritis. The differences between rheumatic and non-rheumatic diseases were significant (p<0.001). The correlation between the two observers was high (p<0.001). CONCLUSIONS: The proposed synovitis score enables stratification of chronic synovitis into low-grade (score 2-4) and high-grade (score >4), which is correlated to the nature of the disease (low-grade to non-rheumatic, high-grade to rheumatic), and it therefore contributes to the diagnosis of rheumatic and non-rheumatic joint diseases

27. LEE A, KASAMA R, EVANGELISTO A, ELFENBEIN Bet FALASCA G: Henoch-Schonlein purpura after etanercept therapy for psoriasis, J.Clin.Rheumatol., Vol. 12(5), 249-251., 2006
    Organism:Division of Rheumatology, the Department of Clinical Medicine, Cooper University Hospital, UMDNJ-Robert Wood Johnson Medical School at Camden, Camden, New Jersey 08103, USA a0868@aolcomFAU - Lee, Annabelle
    Abstract:Etanercept is a recombinant dimeric fusion protein consisting of a tumor necrosis factor-alpha receptor ligand-binding region linked to the Fc portion of human IgG. It is approved for use in the treatment of rheumatoid arthritis, ankylosing spondylitis, juvenile rheumatoid arthritis, psoriasis, and psoriatic arthritis. Since 1998, there have been reports of vasculitic adverse events, including necrotizing vasculitis and leukocytoclastic vasculitis. In addition, the adverse events reporting system of the U.S. Food and Drug Administration has recorded 35 cases of leukocytoclastic vasculitis, 20 after etanercept therapy and 15 after infliximab. Most cases of cutaneous vasculitis describe development of symptoms within 3 months of etanercept use. In only one case report was direct immunofluorescence performed on tissue and no specific immunoreactivity found. We describe the first case of Henoch-Schonlein purpura with acute renal failure associated with increase in etanercept dose after 11 months of use for treatment of psoriasis. Discontinuation of the drug and treatment with a course of systemic steroids led to the complete resolution of the vasculitis and improvement of renal function. Vasculitis occurring even during chronic use of antitumor necrosis factor agents must be considered as possibly related to the therapy

28. LEE DH, DAUD U, WIPFL J, PEPMUELLER PH, DAVITT BVet MOORE TL: The Decreasing Prevalence of Uveitis Associated with Juvenile Rheumatoid Arthritis: Do NSAIDs Play a Role?, J.Clin.Rheumatol., Vol. 9(3), 151-155., 2003
    Organism:From the *Departments of Ophthalmology, daggerInternal Medicine, and double daggerPediatrics, section signDivision of Pediatric Rheumatology, Cardinal Glennon Children's Hospital, St Louis University Health Sciences Center, St Louis, MO 63104
    Abstract:We studied the prevalence and characteristics of chronic uveitis in a population of children diagnosed with juvenile rheumatoid arthritis (JRA). Uveitis is one of the most important, potentially debilitating extra-articular manifestations of JRA and has been observed in as many as 20% of cases. The medical records of 230 patients diagnosed with JRA and treated at a tertiary care hospital ophthalmology clinic between 1992 and 2000 were retrospectively reviewed.Seventeen patients (7.4%) were found to have clinical features of uveitis. There was a preponderance of female patients (16/17) and pauciarticular disease (13/17). Only 12 of 17 were ANA positive. Six had uveitis at diagnosis. Patients who were receiving naproxen had less incidence of uveitis compared with those receiving other nonsteroidal antiinflammatory drugs. Despite a relatively low prevalence of uveitis, complications occurred in about 24% (4/17) of the patients, even with adequate treatment and close monitoring.The prevalence of uveitis in JRA seems to be decreasing and may be secondary to the increased use of naproxen. However, routine ophthalmologic screening should be continued in patients with JRA to avoid potential complications of chronic uveitis

29. LOOS T, DEKEYZER L, STRUYF S, SCHUTYSER E, GIJSBERS K, GOUWY M, FRAEYMAN A, PUT W, RONSSE I, GRILLET B, OPDENAKKER G, DAMME JVet PROOST P: TLR ligands and cytokines induce CXCR3 ligands in endothelial cells: enhanced CXCL9 in autoimmune arthritis, Lab Invest., Vol. 86(9), 902-916., 2006
    Organism:Laboratory of Molecular Immunology, Rega Institute for Medical Research, University of Leuven, Leuven, BelgiumFAU - Loos, Tamara
    Abstract:CXC chemokines are potent attractants of neutrophil granulocytes, T cells or natural killer cells. Toll-like receptors (TLR) recognize microbial components and are also activated by endogenous molecules possibly implicated in autoimmune arthritis. In contrast to CXC chemokine ligand 8 (CXCL8), no CXC chemokine receptor 3 (CXCR3) ligand (ie CXCL9, CXCL10 and CXCL11) was induced by bacterial TLR ligands in human microvascular endothelial cells (HMVEC). However, peptidoglycan (PGN), double-stranded (ds) RNA or lipopolysaccharide (LPS) (TLR2, TLR3 or TLR4 ligands, respectively) synergized with interferon-gamma (IFN-gamma) at inducing CXCL9 and CXCL10. In contrast, enhanced CXCL11 secretion was only obtained when IFN-gamma was combined with TLR3 ligand. Furthermore, flagellin, loxoribine and unmethylated CpG oligonucleotide (TLR5, TLR7 and TLR9 ligands, respectively) did not enhance IFN-gamma-dependent CXCR3 ligand production in HMVEC. In analogy with TLR ligands, tumor necrosis factor-alpha (TNF-alpha) or interleukin-1beta (IL-1beta), in combination with IFN-gamma, synergistically induced CXCL9 and CXCL11 in HMVEC and human fibroblasts, two fundamental cell types delineating the joint cavity. Etanercept, a humanized soluble recombinant p75 TNF-receptor/IgG(1)Fc fusionprotein, neutralized synergistic CXCL9 production induced by TNF-alpha plus IFN-gamma, but not synergy between IFN-gamma and the TLR ligands PGN or LPS. Synovial chemokine concentrations exemplify the physiopathological relevance of the observed in vitro chemokine production patterns. In synovial fluids of patients with spondylarthropathies (ie ankylosing spondylitis or psoriatic arthritis) or rheumatoid arthritis, significantly enhanced CXCL9, but not CXCL11 levels, were detected compared to concentrations in synovial fluids of patients with metabolic crystal-induced arthritis. Thus, CXCL9 is an important chemokine in autoimmune arthritis

30. LOPES M, ROIZENBLATT S, GUILLEMINAULT C, PASSARELLI C, POYARES D et TUFIK S: Sleep cyclic alternating pattern as a marker of chronic pain and sleep loss as a marker of inflammatory process in children, A83, 17-06-2001

31. LOVELL DJ, GLASS D, RANZ J, KRAMER S, HUANG B, SIERRA R, I, HENDERSON CJ, PASSO M, GRAHAM B, BOWYER S, HIGGINS G, RENNEBOHM R, SCHIKLER KNet GIANNINI E: A randomized controlled trial of calcium supplementation to increase bone mineral density in children with juvenile rheumatoid arthritis, Arthritis & Rheumatism, Vol. 54, 2235-2242., 2006
    Organism:Univ Cincinnati, Med Ctr, William S Rowe Div Rheumatol, Childrens Hosp, ML4010,3333 Burnet Ave, Cincinnati, OH 45229 USA USA
    Abstract:Objective. To examine the effects of daily supplementation with calcium (Ca) in combination with vitamin D on total body and lumbar spine bone mineral density (BMD) in patients with juvenile rheumatoid arthritis (JRA) who had not taken corticosteroids for at least 3 months prior to the beginning of the study.Methods. One hundred ninety-eight children and adolescents (141 girls and 57 boys) with JRA, ages 6 to 18 years, with a mean +/- SD age of 11.7 +/- 3.3 years and a mean +/- SD disease duration of 5.6 +/- 3.8 years at the beginning of the study, were enrolled in this randomized double-blind, placebo-controlled trial to receive either daily oral supplements of 1,000 mg of Ca and 400 IU of vitamin D (n = 103) or matched placebo tablets and 400 IU of vitamin D (n = 95) for 24 months. Total body BMD (TBBMD) was measured by dual x-ray absorptiometry at baseline and every 6 months for 24 months.Results. At baseline, the mean +/- SD TBBMD was 0.89 +/- 0.14 gm/cm(2) among patients randomized to the Ca group and 0.87 +/- 0.14 gm/cm(2) among those randomized to placebo (P = 0.445). At 24 months, the mean SD TBBMD among those receiving Ca was 0.95 +/- 0.13 gm/cm(2). compared with 0.92 +/- 0.14 gm/cm(2) among those receiving placebo. A longitudinal random-effects mixed model analysis that controlled for differences in the subject's initial BMD, sex, Tanner stage, adherence to the study medication regimen, and b ody composition revealed significantly higher TBBMD among patients who received Ca compared with patients who received placebo during the study period (P = 0.03).Conclusion. Ca supplementation resulted in a small, but statistically significant, increase in TBBMD compared with placebo in children with JRA

32. LOVELL DJ, REIFF A, JONES OY, SCHNEIDER R, NOCTON J, STEIN LD, GEDALIA A, ILOWITE NT, WALLACE CA, WHITMORE JB, WHITE B, GIANNINI EHet PEDIAT RC: Long-term safety and efficacy of etanercept in children with polyarticular-course juvenile rheumatoid arthritis, Arthritis & Rheumatism, Vol. 54, 1987-1994., 2006
    Organism:Cincinnati Childrens Hosp, Ctr Med, Locat E,Room 2-129,3333 Burnet Ave, Cincinnati, OH 45229 USA USA
    Abstract:Objective. Previous studies showed that etanercept treatment in patients with polyarticular-course juvenile rheumatoid arthritis (JRA) provided rapid clinical improvement that was sustained for up to 2 years. The goal of our study was to provide data on safety and efficacy after 4 years of etanercept treatment in patients with JRA.Methods. Patients with active polyarticular-course JRA who participated in an efficacy study continued etanercept treatment in an open-label extension. Safety was assessed by measuring rates of serious adverse events (SAEs) and serious infections. Efficacy was assessed using the American College. of Rheumatology (ACR) Pediatric 30 criteria for improvement and standard measures of disease activity. (The ACR Pediatric 30 criteria are defined as improvement of >= 30% in at least 3 of 6 core response variables used to assess disease activity, with no more than I variable worsening by >= 30%.)Results. Of the 69 patients who enrolled in the original efficacy study, 58 patients (84%) enrolled in the extension, 34 patients received etanercept treatment for >= 4 years, and 32 of these received complete efficacy assessments. The rate of SAEs was 0.13 per patient-year, and the rate of serious infections was 0.04 per patient-year, in a total etanercept exposure of 225 patient-years. Eighty-two percent of patients who received corticosteroids at any time during the extension were able to decrease their dosage to <= 5 mg/day prednisone equivalent. Of the 32 patients with complete efficacy data who received etanercept for >= 4 years, 94% achieved an ACR Pediatric 30 response and 78% achieved an ACR Pediatric 70 response at the last study visit.Conclusion. Etanercept offers an acceptable safety profile in children with polyarticular-course JRA and provides significant improvement in disease manifestations that are sustained for >= 4 years

33. MACRAE VE, WONG SC, SMITH W, GRACIE A, MCINNES I, GALEA P, GARDNER-MEDWIN J, FARQUHARSON C et AHMED SF: Effects of synovial-fluid and serum from children with juvenile idiopathic arthritis on growth plate chondrocyte dynamics, 1166, 05-07-2001

34. MALEMUD CJ: Growth hormone, VEGF and FGF: Involvement in rheumatoid arthritis|, 2007
    Organism:Adult rheumatoid arthritis (RA), a systemic autoimmune disorder of unknown etiology, is characterized by dysfunctional cellular and humoral immunity, enhanced migration and attachment of peripheral macrophages and pro-inflammatory leukocytes to the synovium and articular cartilage of diarthrodial joints. The progressive destruction of cartilage and bone in RA is a result of elevated pro-inflammatory cytokine gene expression, synovial neovasculari zation, proteinase-mediated dissolution of articular cartilage matrix and osteoclast-mediated subchondral bone resorption. Juvenile chronic arthritis (JCA) is disease with manifestations similar to adult RA that occurs in childhood. JCA usually causes precocious joint destruction and often also presents with evidence of growth plate anomalies and reduced stature. Three proteins play an integral role in both adult RA and JCA. These are somatotropin (also called pituitary growth hormone (GH)), vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF). GH is responsible for regulating long bone growth and skeletal maturation through its capacity to stimulate insulin-like growth factor-I (IGF-1) synthesis by hepatocytes. Mech anisms responsible for growth plate disturbances and short stature in children with JCA include deficient GH production, GH-insensitivity resulting from defects in the GH receptor, suppressed IGF-1 synthesis or neutralization of IGF-1 action by IGF-1 binding proteins (IGFBPs). In addition, GH has also been implicated in perpetuating inflammation and pain in adult RA. VEGF has been shown to be the critical angiogenesis factor responsible for vascular proliferation and blood vessel invasion of the synovial lining membrane in RA. Acidic FGF (FGF-1) and basic FGF (FGF-2) have also been implicated in aberrant synoviocyte proliferation (i.e. synovial hyperplasia) and apoptosis resistance in adult RA. (c) 2006 Elsevier B.V. All rights reserved

35. MATIJEVIC R, STANKOVIC M, NINKOVIC S, SAVIC Det MILANKOV M: [Treatment of knee flexion contracture in patients with chronic juvenile arthritis--a case report], Med.Pregl., Vol. 59(5-6), 273-276., 2006
    Organism:Institut za hirurgiju, Klinika za ortopedsku hirurgiju i traumatologiju, Klinicki centar "Novi Sad", Novi SadFAU - Matijevic, Radmila
    Abstract:INTRODUCTION: Knee flexion contractures are common after-effects of juvenile arthritis. Treatment is usually conservative and may include physical therapy and kinesitherapy. Surgical treatment, particularly of the soft parts, indicated for contractures resistant to conservative treatment, helps to correct the deformity, maintain movements, and relieves pain. Intensive postoperative physiotherapy is of special importance. CASE REPORT: A 23-year-old female patient with chronic juvenile arthritis since the age of one was admitted for treatment of flexion contractures in both knees, muscle hypotrophy, loss of strength and gait disability. The patient underwent arthroscopic synovectomy. The operation was first performed on the right and after 3 mouths on the left knee. The preoperative range of motion in the right knee was 30 degrees - 70 degrees and in the left 40 degrees - 80 degrees. The patient underwent intensive physical therapy to reduce postoperative swelling of knees and firstly passive and then active kinesitherapy. Nine months after the first surgery and six months after the second, the range of motion in the right knee was 0 degrees - 100 degrees and in the left 0 degrees - 105 degrees. The strength of tested muscles was increased and gait was improved. CONCLUSION: Management and rehabilitation of patients with chronic juvenile arthritis include maintenance or improvement in position and function of joints that is achieved with synovectomy. The results depend on combined interdisciplinary rehabilitation, well-experienced staff and pre- and post-operative physiotherapy as well as kinesitherapy. Arthroscopic synovectomy has many advantages and we believe that it was a better solution than open capsulosynovectomy in this patient with chronic juvenile arthritis of the knee

36. MILLER FW: Is occupational exposure to mineral oil a risk factor for rheumatoid arthritis?, Nat.Clin.Pract.Rheumatol., Vol. 2(3), 130-131., 2006
    Organism:Environmental Autoimmunity Group, National Institutes of Health, DHHS, Clinical Research Center, Bethesda, MD 20892-1301, USA millerf@mailnihgovFAU - Miller, Frederick W
    Abstract:

37. MIRANDA LA, BRAGA F, FISCHER RG, SZTAJNBOK FR, FIGUEREDO CMet GUSTAFSSON A: Changes in Periodontal and Rheumatological Conditions After 2 Years in Patients With Juvenile Idiopathic Arthritis, J.Periodontol., Vol. 77(10), 1695-1700., 2006
    Organism:* Institute of Odontology, Division of Periodontology, Karolinska Institute, Huddinge, Sweden, dagger Currently, Graduate Program in Periodontology, Brazilian Lutheran University, Canoas, Rio Grande do Sul, Brazil; previously, Graduate Program in Periodontology, Dental School, Rio de Janeiro State University, Rio de Janeiro, Brazil, double dagger Graduate Program in Periodontology, Dental School, Rio de Janeiro State University, section sign Pediatric Rheumatology Unit, Adolescent Health Care Unit, Rio de Janeiro State University
    Abstract:Background: The aim of this study was to monitor changes in periodontal inflammation in patients with juvenile idiopathic arthritis (JIA) for 2 years. We investigated the influence of rheumatic disease activity and antirheumatic medication on clinical and immunological parameters of periodontal inflammation in these individuals. Methods: Two years after a baseline examination, the periodontal and rheumatological conditions of 18 adolescents with JIA and 14 control subjects were described. The clinical periodontal inflammation was monitored by registration of visual plaque, marginal bleeding, probing depth, and clinical attachment loss (AL). Periodontal inflammation was also assessed by analysis of the cytokines interleukin (IL)-1beta and IL-18 and the collagenase matrix metalloproteinase (MMP)-8 by enzyme-linked immunosorbent assay. Results: The erythrocyte sedimentation rate and clinical rheumatological parameters were significantly improved at the 2-year follow-up. The number of sites with plaque decreased, and the number of pockets >/=4 mm increased, whereas bleeding levels and the extension of AL remained unchanged. IL-1beta in gingival crevicular fluid decreased significantly in the JIA group after 2 years. No differences were observed for IL-1beta, MMP-8, or IL-18 levels between groups after 2 years. Conclusion: Two years after the baseline examination, no clinical or laboratory differences in periodontal inflammation could be found between JIA patients and control subjects

38. MORI M, TAKEI S, IMAGAWA T, IMANAKA H, MAENO N, KUROSAWA R, KAWANO Yet YOKOTA S: Pharmacokinetics, efficacy, and safety of short-term (12 weeks) etanercept for methotrexate-refractory polyarticular juvenile idiopathic arthritis in Japan, Mod.Rheumatol., Vol. 15(6), 397-404., 2005
    Organism:Department of Pediatrics, Yokohama City University School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, 236-0004, Japan, mmori@medyokohama-cuacjpFAU - Mori, Masaaki
    Abstract:We examined and evaluated the pharmacokinetics, efficacy, and safety of etanercept in patients with methotrexate (MTX)-refractory polyarticular juvenile idiopathic arthritis (JIA) in Japan. All MTX-refractory polyarticular JIA patients 4-17 years old received 0.4 mg of etanercept per kilogram of body weight subcutaneously twice weekly for up to 3 months in the open-label, prospective, and multicenter trial. A response was defined as an improvement of 30%, 50%, 70%, or more from baseline in at least three of six indicators of disease activity, with no more than one indicator worsening by more than 30% from baseline (30%, 50%, or 70% definition of improvement, respectively), and disease activity score (DAS28) by EULAR (European League Against Rheumatism) response criteria. At the end of the 12-week study, 20 of the 22 patients (90.9%) had responses with both 30% and 50% definition of improvement after etanercept treatment. To our surprise, 15 of 22 patients (68.2%) had a response with 70% definition of improvement. Moreover, in DAS28, eight patients were evaluated as having a good response and there were no patients with a poor response to etanercept. Treatment had to be stopped in one patient who developed joint contracture during the study period, but there were no significant adverse events in the other patients. In conclusion, treatment with etanercept leads to significant improvement in patients with active polyarticular JIA in Japan. Etanercept is well tolerated by pediatric patients as well as adults

39. NISHIMOTO Net KISHIMOTO T: Interleukin 6: from bench to bedside, Nat.Clin.Pract.Rheumatol., Vol. 2(11), 619-626., 2006
    Organism:N Nishimoto and T Kishimoto are professors in the Laboratory of Immune Regulation in the Graduate School of Frontier Biosciences, Osaka University, Suita City, JapanFAU - Nishimoto, Norihiro
    Abstract:Interleukin (IL)-6 is a pleiotropic cytokine that has important roles in the regulation of the immune response, inflammation, and hematopoiesis. Disruption of IL-6 regulation might, however, affect the immune response and consequently induce immune-mediated inflammatory diseases such as rheumatoid arthritis, systemic juvenile idiopathic arthritis, Castleman disease, and Crohn's disease. Overproduction of IL-6 also contributes, through its roles as a growth factor or an antiapoptotic factor, to the development of malignant diseases such as multiple myeloma and renal cancer. Progress in the study of IL-6 has increased our understanding of the pathological roles of this cytokine in these diseases and provided key evidence that antagonizing its activities can be used as a therapeutic strategy. The application of molecular biology techniques to design monoclonal antibodies as therapeutic agents has made it possible to regulate the IL-6 signal to successfully treat diseases that have so far proved refractory to conventional therapies. Blocking IL-6 actions by use of a humanized antibody, tocilizumab, which targets the IL-6 receptor, has been proven to be therapeutically effective for rheumatoid arthritis, systemic juvenile idiopathic arthritis, Castleman disease and Crohn's disease. In this review, we discuss a paradigm of IL-6 from basic science to clinical use

40. NYGARD K, BRANTSAETER ABet MEHL R: Disseminated and chronic Lyme borreliosis in Norway, 1995 - 2004, Euro.Surveill., Vol. 10(10), 235-238., 2005
    Organism:Norwegian Institute of Public Health, Division of Infectious Disease Control, Oslo, NorwayFAU - Nygard, K
    Abstract:Lyme borreliosis is the most common tickborne infection in Norway. All clinical manifestations of Lyme borreliosis other than erythema migrans are notifiable to Folkehelseinstituttet, the Norwegian Institute of Public Health. During the period 1995-2004 a total of 1506 cases of disseminated and chronic Lyme borreliosis were reported. Serological tests were the basis for laboratory diagnosis in almost all cases. The annual numbers of cases showed no clear trend over the period, but varied each year between 120 and 253 cases, with the highest number of cases reported in 2004. Seventy five per cent of cases with information on time of onset were in patients who fell ill during the months of June to October. There was marked geographical variation in reported incidence rates, with the highest rates reported from coastal counties in southern and central Norway. Fifty six per cent of the cases were in males and 44% in females. The highest incidence rate was found in children aged between 5 and 9 years. Neuroborreliosis was the most common clinical manifestation (71%), followed by arthritis/arthralgia (22%) and acrodermatitis chronica atrophicans (5%). Forty six per cent of patients were admitted to hospital. Prevention of borreliosis in Norway relies on measures to prevent tick bites, such as use of protective clothing and insect repellents, and early detection and removal of ticks. Antibiotics are generally not recommended for prophylaxis after tick bites in Norway

41. PACKHAM JC: Overview of the psychosocial concerns of young adults with juvenile arthritis, Musculoskeletal.Care., Vol. 2(1), 6-16., 2004
    Organism:Staffordshire Rheumatology Centre, Haywood Hospital, Stoke-on-TrentFAU - Packham, Jon C
    Abstract:Young adults who develop juvenile idiopathic arthritis in childhood have a significant risk of long-term morbidity and continuing disease activity in adulthood. The impact of a physically restricting and painful chronic illness can make the transition from adolescence to adulthood more challenging.In this overview of the psychological and social impact of juvenile arthritis on young adults, particular attention is given to those areas that are of concern to this age group. The transition from adolescence to adulthood can be detrimentally affected not only by the attitudes of peers and parents, but also by the attitudes of the individual with arthritis. Chronic arthritis, including juvenile arthritis, is related to increased rates of anxiety and depression. In the face of functional restriction, pain, and poor body image, social and sexual relationships may be harder to develop and maintain. The family of the young adult may also be affected on many levels. Employment and financial security are common and well-founded concerns of young disabled adults. Copyright (c) 2004 Whurr Publishers Ltd

42. PAUL-PLETZER K: Tocilizumab: Blockade of interleukin-6 signaling pathway as a therapeutic strategy for inflammatory disorders, Drugs Today (Barc.)., Vol. 42(9), 559-576., 2006
    Organism:Medical Information Department, Prous Science, Barcelona, Spain journals@prouscomFAU - Paul-Pletzer, Kalanethee
    Abstract:Interleukin (IL)-6 contributes to a myriad of physiologic and pathophysiologic processes. Among its many physiologic functions, IL-6 plays an active role in immunology, inflammatory responses, bone metabolism, arthritis and neoplasia. Overproduction of IL-6 has been implicated in the disease pathology of several inflammatory and autoimmune disorders, including rheumatoid arthritis, Castleman's disease, Crohn's disease and systemic-onset juvenile idiopathic arthritis. Interception of the IL-6 signaling pathway could thus represent a new treatment option for these diseases, given their refractory status to conventional therapy. Clinical studies with tocilizumab, a humanized monoclonal anti-IL-6 receptor antibody, have been undertaken to explore this option. Current short-term results indicate that tocilizumab dramatically improves disease activity and is well tolerated. Further long-term safety and efficacy studies are needed to confirm the therapeutic benefit of this antibody in inflammatory and autoimmune disorders. (c) 2006 Prous Science. All rights reserved

43. PEDERSEN M, JACOBSEN S, KLARLUND Met FRISCH M: Socioeconomic status and risk of rheumatoid arthritis: a Danish case-control study, J.Rheumatol., Vol. 33(6), 1069-1074., 2006
    Organism:Department of Epidemiology Research, Danish Epidemiology Science Centre, Statens Serum Insitut, DK-2300 Kobenhavn S, Denmark mtb@ssidkFAU - Pedersen, Merete
    Abstract:OBJECTIVE: To examine whether markers of socioeconomic status (SES) are associated with risk of rheumatoid arthritis (RA), and if so, whether selected lifestyle-related factors could explain this association. METHODS: We conducted a frequency matched case-control study; subjects comprised 515 patients (participation rate 83%) attending rheumatology and internal medicine departments in Denmark, with recently diagnosed RA according to the American College of Rheumatology (ACR) 1987 classification criteria for RA (mean disease duration 2.3 yrs), and 769 frequency-matched population controls (participation rate 64%). Information about SES and environmental exposure was obtained by structured telephone interview. Logistic regression analyses evaluated the role of markers of SES. RESULTS: Level of education was significantly inversely associated with risk of RA, with a 2-fold lower risk of RA among those with the longest formal education compared with those having the lowest level of education (multivariate odds ratio = 0.43, 95% confidence interval 0.24-0.76, p trend = 0.001). None of a series of studied lifestyle factors could explain this finding in multivariate logistic regression analyses. When dividing the RA cases into clinical subgroups, the inverse association with level of education was found to apply predominantly to rheumatoid factor (RF)-positive RA. CONCLUSION: The inverse association between level of education and risk of RF-positive RA was not explained by any of the examined lifestyle factors. RF-positive and RF-negative RA may be 2 distinct diseases with different etiologies, with unmeasured factors related to educational level predominantly associated with the risk of RF-positive RA. However, because mechanisms underlying referral to a hospital might be linked to educational level, our observation based on hospital-referred RA patients should be evaluated cautiously. The study stresses the importance of taking SES measures into account in studies that aim at identifying environmental risk factors for RA

44. POURBAGHER A, POURBAGHER MA, SAVAS L, TURUNC T, DEMIROGLU YZ, EROL Iet YALCINTAS D: Epidemiologic, clinical, and imaging findings in brucellosis patients with osteoarticular involvement, AJR Am.J.Roentgenol., Vol. 187(4), 873-880., 2006
    Organism:Department of Radiology, Baskent University Adana Teaching and Medical Research Center, Dadaloglu Mah, 39 Sok No 6, Yuregir, 01250 Adana, TurkeyFAU - Pourbagher, Aysin
    Abstract:OBJECTIVE: The aim of this study was to assess the epidemiologic and clinical features, complications, imaging findings, and outcomes for brucellosis patients with osteoarticular involvement. SUBJECTS AND METHODS: This prospective study was performed over 4 years (December 2000-December 2004). The subjects were 251 Turkish patients (age range, 2-77 years) who were diagnosed with brucellosis during that period. Joint sonography, radiography, radionuclide bone scintigraphy, and MRI were performed in all patients with osteoarticular and spinal manifestations. RESULTS: The disease was acute in 92 patients (36.7%), subacute in 48 patients (19.1%), and chronic in 111 patients (44.2%). Sonography of the joints showed bursitis in 13 patients (5.2%). Radiography, MRI, and scintigraphy revealed 71 patients (28.3%) with sacroiliitis, 26 (10.4%) with spondylodiskitis, three (1.2%) with acute osteomyelitis, and one (0.4%) with avascular necrosis of the femoral head. All patients received combinations of either two or three antibiotics. Surgery was performed in three patients with spinal instability or radiculopathy. CONCLUSION: Brucellosis is endemic to some regions. MRI is the method of choice for diagnosing osteoarticular and spinal complications of human brucellosis, especially during the early phase. It is important to differentiate tuberculous spondylodiskitis from brucellar spondylodiskitis because proper treatment for each of these diseases can prevent complications. The radiologic findings for these two forms of spondylodiskitis are similar, so serologic testing for brucellosis is necessary in such cases

45. RAO SK, RAO Set NAIK AM: A descriptive clinical evaluation of arthroscopic synovectomy in rheumatoid knees: a prospective study, Ceylon Med.J., Vol. 51(1), 7-9., 2006
    Organism:Department of Orthopaedics, Kasturba Medical College, Manipal, Karnataka, India skraok@yahoocomFAU - Rao, Sharath K
    Abstract:OBJECTIVE: To evaluate the clinical outcome of arthroscopic synovectomy for persistent rheumatoid synovitis of the knee joints. DESIGN: Prospective clinical study. SETTING: Kasturba Medical College Hospital, Manipal. PATIENTS: Fifty two knee joints in 46 patients. MEASUREMENTS: The effect of the procedure and its influence in the progression of the disease process on knee joints were assessed in terms of reduction of pain, improvement in range of motion, improvement in functional activity and recurrence of synovitis with effusion. RESULTS: During the average follow up period of 5 years, the patients showed appreciable improvement (90% of knee joints) until 3 years of follow up. At the end of 5 years of follow up, it reduced to about 75%. CONCLUSIONS: Arthroscopic synovectomy along with medical treatment can control the disease process and preserve the knee joint function for up to 3 years

46. RODGERS GL, MORTENSEN JEet GOLDSMITH DP: Pyogenic Arthritis Caused by Capnocytophaga Gingivalis in an Immunocompetent Three-Year-Old Male, J.Clin.Rheumatol., Vol. 7(4), 265-267., 2001
    Organism:Section of Infectious Diseases (GLR) and Section of Rheumatology (DPG), Department of Pediatrics, Department of Pathology and Laboratory Medicine (JEM), MCP Hahnemann University School of Medicine, St Christopher's Hospital for Children, Philadelphia, PA
    Abstract:Capnocytophaga gingivalis is most often isolated as normal oral flora or with periodontal disease. This organism is also associated with sepsis usually in immunocompromised hosts. We identified pyogenic arthritis caused by C. gingivalis in a 3-year-old immunocompetent male, whose clinical course closely resembled monoarticular onset pauciarticular juvenile rheumatoid arthritis. This is the first report of C. gingivalis septic arthritis in the world literature, but there are increasing reports of infections with this carbon dioxide-loving organism at other sites in nonimmunocompromised individuals. The subacute presentation of the monoarthritis with this organism of low virulence led to a long delay in diagnosis and treatment. Any monoarthritis must continue to raise concern about infection

47. ROSSI F, DI DIA F, GALIPO O, PISTORIO A, VALLE M, MAGNI-MANZONI S, RUPERTO N, TOMA P, MARTINI Aet RAVELLI A: Use of the sharp and larsen scoring methods in the assessment of radiographic progression in juvenile idiopathic arthritis, Arthritis Rheum., Vol. 55(5), 717-723., 2006
    Organism:Istituto di Ricovero e Cura a Carattere Scientifico G Gaslini, Genoa, ItalyFAU - Rossi, Federica
    Abstract:OBJECTIVE: To investigate the applicability of the Sharp and Larsen scoring methods for radiographic damage in juvenile idiopathic arthritis (JIA). METHODS: Wrist/hand radiographs of 25 patients with polyarthritis obtained at first observation and then yearly for 4-5 years were assessed independently by 2 pediatric rheumatologists according to the Sharp and Larsen methods. To facilitate score assignment, each patient radiograph was compared with a bone age-related standard. A third pediatric rheumatologist measured the Poznanski score, and a pediatric radiologist provided a semiquantitative assessment of radiographic damage severity. RESULTS: Interobserver and intraobserver agreement on longitudinal scores were good for both Sharp and Larsen methods, with intraclass correlation coefficient >0.9. Agreement on change assessment was good for the Sharp method and moderate for the Larsen method. Both methods yielded a steady increase in scores during the study, with score change being more marked in the first year. Sharp and Larsen scores were highly correlated (r(s) = 0.96). Correlations of both scores with the Poznanski score were moderate to high (r(s) from -0.62 to -0.72). Radiologist score was correlated at borderline-high level with both Sharp (r(s) = 0.70) and Larsen (r(s) = 0.71) scores. Sharp and Larsen score change from baseline to final visit was moderately to highly correlated with the number of joints with active arthritis and restricted motion and the Childhood Health Assessment Questionnaire score at final visit. CONCLUSION: Our results demonstrate that the Sharp and Larsen scoring systems are potentially reliable and valid for assessment of radiographic progression in patients with polyarticular JIA

48. SAKIMURA K, OMORI T, IWASHITA E, YOSHIDA T, TSUZUKI Y, FUJIMORI K, KONISHI F, YOSHIDA Y, ANZAI H, SUZUKI H, SUGAWARA S, TAKEDA Y, HIRAISHI K, SANIABADI AR, IDE T, MIURA Set OTA S: Clinical response is associated with elevated plasma interleukin-1 receptor antagonist during selective granulocyte and monocyte apheresis in patients with ulcerative colitis, Dig.Dis.Sci., Vol. 51(9), 1525-1531., 2006
    Organism:Department of Internal Medicine, Saitama Red Cross Hospital, Saitama, JapanFAU - Sakimura, Kyoya
    Abstract:Depletion of granulocytes and monocytes (GM) by selective apheresis (GMA) with an Adacolumn exerts an anti-inflammatory effect in patients with ulcerative colitis (UC) or rheumatoid arthritis. However, the mechanism of the anti-inflammatory effect of GMA is not fully understood yet. We investigated the effect of GMA on the plasma concentration of interleukin-1 receptor antagonist (IL-1ra), a potent anti-inflammatory cytokine. Twenty-six patients with active UC received GMA at one session per week for 5 consecutive weeks. Clinical response was defined as Deltaclinical activity index (DeltaCAI=CAI at entry - CAI at post)>or=4, while clinical remission was defined as CAI<or=4. Twenty-one of twenty-six patients (80.8%) responded to GMA. In the first session, plasma from responder patients showed a significant (P < 0.01) increase in IL-1ra in the Adacolumn outflow. In contrast, there was no change in IL-1ra in nonresponders. In conclusion, release of IL-1ra during GMA might be one mechanism of clinical efficacy associated with this therapy

49. SZENBORN Let CZERNIAK T: PFAPA syndrome (periodic fever, aphthous stomatitis, pharyngitis, cervical adenopathy) - Own experience|, 2006
    Organism:PFAPA syndrome is characterized by periodic episodes of high fever (> 39degreesC) lasting 3 to 6 days and recurring every 21 to 28 days, accompanied by aphthous stomatitis, pharyngitis and cervical adenopathy. Most cases occur in children under 5 years of age. Not all children manifest all three signs beside fever. PFAPA is defined clinically, because specific laboratory abnormalities have not been found. The episodes of PFAPA may last for years and the patient is well between episodes. The cause of PFAPA is unknown and there are no reported complications. PFAPA is sporadic, and no ethnic predilection was found. We describe 3 cases of PFAPA syndrome in boys aged 6 to 10 years. They all had typical symptoms of PFAPA. During the periods of fever, an inflammatory syndrome with hyperleucocytosis and a marked increase in C-reactive protein (CRP) levels and sedimentation rate were observed. After excluding the presence of an acute infection, other possible reasons for fever including cyclic neutropenia, juvenile rheumatoid arthritis, hyperimmunoglobulin D syndrome and familial Mediterranean fever were excluded. We observed a progressive decrease in the incidence of periodic fever and an absence of complications. By one patient the symptoms resolved spontaneously within 3 years, by the other one after adenotomy, the third one has still mild symptoms not requiring any therapy. No complications were observed. (c) 2006 by Polskie Towarzystwo Pediatryczne

50. TIFTIKCI A, OZDEMIR A, TARCIN O, TARCIN O, INANC N, SAHINOGLU S, DIRESKENELI H, YAVUZ S, URAS Fet BARUT Y: Influence of serum folic acid levels on plasma homocysteine concentrations in patients with rheumatoid arthritis, Rheumatol.Int., Vol. 26(3), 191-194., 2006
    Organism:Internal Medicine Department, Haydarpasa Numune Hospital, Istanbul, Turkey arzutiftikci@hotmailcomFAU - Tiftikci, Arzu
    Abstract:The purpose of this study was to investigate whether negative effects of methotrexate (mtx) on blood homocysteine (hmc) levels can be prevented with the replacement of folic acid. 42 female patients with rheumatoid arthritis (RA) were studied. Patients were separated into two groups according to their treatment status with mtx (group I: 27 patients taking mtx and folic acid; group II: 15 patients not using mtx). The level of hmc was found to be 6.3+/-2.4 micromol/l in group I and 7.87+/-3.2 micromol/l in group II (p>0.05). Folic acid levels of group I and II were found to be 21.3+/-15.9 ng/ml and 8.41+/-2.86 ng/ml respectively (p<0.001). There was a statistically-significant correlation between age and hmc levels (r=0.386, p=0.012). Negative statistically-significant correlations were observed between folic acid and hmc levels. The effects of mtx on hmc can be prevented with the replacement of folic acid

51. TRISTANO AG, CASANOVA-ESCALONA L, TORRES Aet RODRIGUEZ MA: Macrophage Activation Syndrome in a Patient with Systemic Onset Rheumatoid Arthritis: Rescue with Intravenous Immunoglobulin Therapy, J.Clin.Rheumatol., Vol. 9(4), 253-258., 2003
    Organism:From the *Centro Nacional de Enfermedades Reumaticas, Hospital Universitario de Caracas, Caracas, Venezuela; and daggerCentro Medico "Guerra Mendez," Valencia, Venezuela
    Abstract:We report the case of a 7-year-old boy with systemic onset juvenile rheumatoid arthritis (JRA) who developed macrophage activation syndrome during a period of relative remission. He presented with high-grade fever, enlarged lymph nodes, acute hepatitis, severe pancytopenia, and evidence of disseminated intravascular coagulopathy. He became severely ill, with persistent mucosal bleeding, hypovolemia, and vascular instability, and he was admitted to the intensive care unit. No response was observed to treatment with high-dose intravenous corticosteroids and blood product replacements, but the patient fully recovered after the completion of two pulses of intravenous immunoglobulin. This treatment modality may be an alternative to anti-TNF-alpha and cyclosporine A for a prompt response in JRA patients with this potentially fatal condition

52. TYNJALA P, LINDAHL P, HONKANEN V, LAHDENNE Pet KOTANIEMI K: Infliximab and etanercept in the treatment of chronic uveitis associated with refractory juvenile idiopathic arthritis, Ann.Rheum.Dis., Vol. ., 2006
    Organism:Helsinki University Central Hospital, the Hospital for Children and Adolescents, Finland
    Abstract:OBJECTIVE: Evaluation of the anti-tumor necrosis factor (TNF) therapy on juvenile idiopathic arthritis (JIA)-associated uveitis. METHODS: Twenty-four patients with uveitis were on etanercept and twenty-one on infliximab. The end- point ophthalmologic evaluation was at 24 months or at the termination of the first biological agent. The ocular inflammatory activity was graded based on the number of anterior chamber cells. RESULTS: Of the 45 patients, uveitis improved in 14 (31%), no change was observed in 14 (31%), and in 17 (38%) the activity of uveitis increased. Inflammatory activity improved more frequently (p=0.047) in the patients on infliximab than on etanercept. The number of uveitis flares/year was higher (p=0.015) in the patients on etanercept (mean 1.4, range 0-3.2) compared to infliximab (mean 0.7, range 0-2.0). Uveitis developed for the first time while on anti-TNF therapy in five patients - four on etanercept (2.2 /100 patient-years) and one on infliximab (1.1 /100 patient-years). CONCLUSIONS: During anti-TNF therapy, the ophthalmologic condition improved in one-third of the patients with uveitis. In chronic anterior uveitis, associated with refractory JIA, infliximab may be more effective than etanercept

53. UUSIMAA P, KROGERUS ML, AIRAKSINEN J, LINNALUOTO M, TERVONEN Oet HAKALA M: Aortic valve insufficiency in patients with chronic rheumatic diseases, Clin.Rheumatol., Vol. 25(3), 309-313., 2006
    Organism:Department of Internal Medicine, University of Oulu, PO Box 5000, 90014 Oulu, Finland paavouusimaa@oulufiFAU - Uusimaa, Paavo
    Abstract:Aortic valve lesions are often found in patients with rheumatic diseases, but their clinical significance has not been properly evaluated. In the present study, the echocardiographic files of the cardiology unit of the Oulu University Hospital were screened for a diagnosis of aortic insufficiency (AI). The aetiology of the valve disease and specific details of the rheumatic disease were evaluated in 160 patients. Twenty-eight patients (18%) had a history of rheumatic fever. Rheumatic disease was found in 14 patients (8.8%) with AI, which is significantly more than the prevalence of rheumatic diseases (1.8%) in the corresponding age group (35-100 years) in Finland. Rheumatoid arthritis or juvenile rheumatoid arthritis was found in seven patients (4.4%), whereas ankylosing spondylitis or seronegative spondylarthropathy were found in four patients (2.5%). Other rheumatic diseases included Takayasu's arteritis (two patients) and scleroderma (one patient). When 38 patients with pure AI without other possible aetiology were analysed, rheumatic disease was found in five patients (13%). Patients with rheumatic disease as a potential aetiology of AI often had symptomatic valve disease, which required surgical treatment, although great differences between different aetiologies were not found

54. VALDES P, CERES L, ALONSO Iet MORENO E: [Sarcoidosis as an uncommon cause of articular pathology in pediatric patients], Radiologia., Vol. 48(1), 37-40., 2006
    Organism:Servicio de Radiodiagnostico, Hospital Costa del Sol, Marbella, Malaga, EspanaFAU - Valdes, Pablo
    Abstract:We present two cases of sarcoidosis with chronic arthropathy presenting clinical and imaging findings compatible with chronic juvenile arthritis. One patient suffered from chronic nephropathy, with anomalous US pattern and sarcoid granulomas demonstrated at renal biopsy. Throughout the illness, the patient suffered from cutaneous lesions that proved to be sarcoid granulomas after biopsy. US and color-Doppler US were useful in detecting the lesions and in the follow-up of the chronic articular pathology in these children. Although sarcoidosis is uncommon, it is important to consider this disease in the diagnosis of chronic arthropathy in children. We analyze these two cases and comment on the clinical and imaging characteristics of pediatric articular sarcoidosis

55. XU M, ROBERTS B, BUSBY B, JACK R, FINN LS, EMERY H et RUTLEDGE JC: Evaluation of multiplex anti-nuclear antibody assay in pediatric patients, A147, 23-07-2001

56. YOKOTA S, MIYAMAE T, IMAGAWA T, IWATA N, KATAKURA Set MORI M: Inflammatory cytokines and systemic-onset juvenile idiopathic arthritis, Mod.Rheumatol., Vol. 14(1), 12-17., 2004
    Organism:Department of Pediatrics, Yokohama City University School of Medicines, 3-9 Fukuura, Kanazawa-ku, Yokohama, 236-0004, Japan, syokota@medyokohama-cuacjpFAU - Yokota, Shumpei
    Abstract:Systemic-onset juvenile idiopathic arthritis (JIA) is a severe and steroid-dependent disease, which sometimes progresses to the fatal disease macrophage activation syndrome. An investigation of inflammatory cytokine levels revealed increases in IL-6 in serum of systemic-onset disease patients. Continuously elevated levels of IL-6 in serum may play a important role in manifesting the clinical symptoms and signs of systemic-onset JIA, including spiking fever, rash, arthritis, and serositis. The characteristic fever spikes parallel IL-6 levels. Long-term exposure to high levels of IL-6 in children results in severe growth impairment, which was strongly suggested by the recent establishment of IL-6 transgenic mice. To avoid disease progression to macrophage activation syndrome and the adverse effects of high-dose corticosteroids, it might be reasonable to inhibit the formation of IL-6/IL-6R complex in order to block the binding to gp130 receptor, a biologically active receptor for IL-6. This review will provide evidence of the relationship between IL-6 homeostasis and systemic-onset JIA, and our recent trials of anti-IL-6R antibody (MRA) for children with acute systemic disease intractable to long-term and high-dose corticosteroid therapy. MRA could be a therapeutic modality for children with systemic-onset JIA intractable to high-dose corticosteroids

57. ZENONE T: Fever of unknown origin in adults: evaluation of 144 cases in a non-university hospital, Scand.J.Infect.Dis., Vol. 38(8), 632-638., 2006
    Organism:Department of Medicine, Unit of Internal Medicine, Centre Hospitalier de Valence, France tzenone@ch-valencefrFAU - Zenone, Thierry
    Abstract:The spectrum of diseases found in series of fever of unknown origin shows variation in relation to selection bias; particularly, selection of the most difficult cases in tertiary reference university centres. We present a series of 144 patients presenting to a non-university hospital between 1999 and 2005 (secondary level of the health care system) with a community-acquired fever of unknown origin. In 37 cases (25.7%), the reason for fever could not be explained. Among the 107 patients with a final diagnosis (74.3%), non-infectious inflammatory disorders represented the most prevalent category (35.5%), surpassing infections (30.8%), miscellaneous causes (20.6%) and malignancies (13.5%). 13 entities accounted for over 68% of diagnoses (sinusitis and occult dental infections, Q fever, Epstein-Barr virus and cytomegalovirus infections, lymphoma, colo-rectal adenocarcinoma, adult-onset Still disease, systemic lupus erythematosus, giant cell arteritis and/or polymyalgia rheumatica, rheumatoid arthritis, polyarteritis nodosa, factitious fever and habitual hyperthermia). As demonstrated in other studies, non-infectious inflammatory diseases emerge as the most prevalent diagnostic category. Giant cell arteritis and polymyalgia rheumatica were particularly frequent in the elderly. Epstein-Barr virus and cytomegalovirus infections and habitual hyperthermia were particularly frequent in the youngest patients. There were no major differences in repartition of diagnostic categories between this series and historical university series

58. ZLOCHA J, KOVACS L, POZGAYOVA S, KUPCOVA Vet DURINOVA S: [Molecular genetic diagnostics and screening of hereditary hemochromatosis], Vnitr.Lek., Vol. 52(6), 602-608., 2006
    Organism:II detska klinika Lekarskej fakulty UK a Detskej fakultnej nemocnice s poliklinikou, Bratislava, Slovenska republika zlocha@dfnspskFAU - Zlocha, J
    Abstract:BACKGROUND: Hereditary hemochromatosis is considered one of the most common hereditary diseases in population of Caucasian origin. In recent years, a candidate gene for HLA-linked hemochromatosis, HFE, has been cloned, and a single G-to-A mutation resulting in a cysteine-to-tyrosine substitution (C282Y) has been identified in up to 80% of study patients with type 1 hereditary hemochromatosis. The purpose of the paper was to confirm the importance of genetic testing for HFE mutations in making the diagnosis of hemochromatosis and find out a suitable diagnostic algorithm for the indication of this form of diagnostics in patients suspected of hereditary hemochromatosis. PATIENTS AND METHODS: The examination of C282Y mutation was conducted in 500 subjects. The most frequent indications for DNA analysis were hepatopathy of unknown ethiology, liver cirrhosis, diabetes mellitus, bronze skin pigmentation in connection with high serum iron concentration, elevated transferrin saturation and elevated serum ferritin levels. RESULTS: In our group of patients, 29 homozygotes and 75 heterozygotes for C282Y mutation were identified, 10 patients carried both C282Y and H63D mutations of HFE gene (compound heterozygotes), whereas in 386 subjects the mutation was not found. The genotype-phenotype correlation showed that 22 homozygotes had liver affection proved by imaging and/or histologic methods. Except the liver disorders, the most common symptoms of these patients were type 2 diabetes mellitus or glucose tolerance disorder (10 patients), arthritis or joint pain (9 patients) and cardiovascular disorders, such as cardiomyopathy (2 patients). Bronze skin pigmentation was present in 9 homozygotes. Transferin saturation values were significantly higher in homozygotes for C282Y mutation as compared to C282Y heterozygotes (p < 0.001), C282Y/H63D compound heterozygotes (p < 0.05) or wild type subjects (p < 0.001) respectively. Also serum ferritin levels were significantly higher in homozygotes for C282Y mutation as compared to C282Y heterozygotes (p < 0.001), C282Y/H63D compound heterozygotes (p < 0.001) and wild type subjects (p < 0.001) respectively. CONCLUSIONS: Our observations confirm that DNA analysis significantly contributes to differential diagnostics of this severe, but in early recognition curable disease. Early detection and phlebotomy treatment prior to the onset of cirrhosis can reduce morbidity and normalize life expectancy. It is readily identified through biochemical testing for iron overload using serum transferrin saturation and genetic testing for C282Y homozygosity. DNA analysis is recommended in patients whose transferrin saturation is 45% or more on a repeated test. General population screening has been waived in preference to targeting high-risk groups such as first-degree relatives of affected individuals and those with secondary iron overload, especially patients with chronic liver disorders and chronic anemia. This screening strategy is likely to continue until uncertainties regarding the natural history of the disease, age-related penetrance, and management of asymptomatic individuals are clarified