Bibliography January 04

1. ALSAEID K, HAIDER MZ, AYOUB EM: Angiotensin converting enzyme gene insertion-deletion polymorphism is associated with juvenile rheumatoid arthritis. J Rheumatol 30:12 2705-2709, 2003
   Organism: Department of Pediatrics, Faculty of Medicine, Kuwait University, Safat 13110, KuwaitFAU - Alsaeid, Khaled
   Abstract: OBJECTIVE: To investigate the incidence of angiotensin converting enzyme (ACE) gene insertion-deletion (I/D) polymorphism genotypes in children with juvenile rheumatoid arthritis (JRA), a heterogeneous chronic disease with autoimmune pathology. ACE gene I/D polymorphism influences the plasma and tissue levels of ACE and has an involvement in inflammatory mechanisms. METHODS: The incidence of ACE gene I/D polymorphism genotypes was determined in 82 children with JRA from Kuwait and compared to that in 48 ethnically matched healthy controls using polymerase chain reaction. RESULTS: A considerably higher incidence of II genotype was observed in the JRA patients compared to controls (p < 0.003). In contrast, no statistically significant difference was detected in the incidence of DD and ID genotypes in JRA patients and controls (p = 0.276 and 0.460, respectively). The incidence of ACE gene polymorphism genotypes was also studied in clinical subclasses of JRA patients and controls. There was no significant difference in the incidence of DD and ID genotypes in either of the 3 JRA subclasses (oligoarticular, polyarticular, and systemic) when compared to controls. However, the incidence of II genotype was found to be significantly higher in all the 3 JRA subclasses compared to controls. The strongest association between II genotype and JRA subclasses was detected in systemic JRA, followed by oligoarticular and polyarticular JRA. This was also reflected in a higher prevalence of I-allele in the systemic JRA cases (13/26, 50%) compared to the D-allele (11/26, 42%). In contrast, D-allele of the ACE gene was more prevalent in oligoarticular and polyarticular JRA cases, than the I-allele (61% and 58%, respectively). CONCLUSION: Our data suggest a significant association of the I-allele of the ACE gene I/D polymorphism with the 3 clinical subclasses of JRA in children, and the highest association was observed in systemic JRA cases

2. ALSUFYANI K, ORTIZ-ALVAREZ O, CABRAL DA, TUCKER LB, PETTY RE, MALLESON PN: The role of subcutaneous administration of methotrexate in children with juvenile idiopathic arthritis who have failed oral methotrexate. J Rheumatol 31:1 179-182, 2004
   Organism: Division of Rheumatology, Department of Pediatrics, University of British Columbia, Vancouver, BC, CanadaFAU - Alsufyani, Khayriah
   Abstract: OBJECTIVE: To describe the outcome of patients with juvenile idiopathic arthritis (JIA) treated with subcutaneous (Sc) methotrexate (MTX) after failing oral MTX (either because of inefficacy or toxicity) in a clinic population. METHODS: The study cohort was identified from our clinical database, and consisted of 61 children with JIA treated with MTX between 1988-2001. All patients fulfilled International League Against Rheumatism (ILAR) criteria for JIA and had disease duration of >/= 6 months and 3 or more active joints before institution of MTX. All patients had a core set of outcome variables assessed at baseline and at 3 months after achieving both maximum oral and SC MTX. Outcome variables included physician global assessment of disease activity, number of active joints, number of joints with limited range of motion, duration of early morning stiffness, and erythrocyte sedimentation rate (ESR). Improvement was defined as at least 30% improvement from baseline in 3 of 5 variables in the core set, with no more than one of the remaining variables worsening by more than 30%. RESULTS: A total of 61 patients, 43 females and 18 males with JIA were studied. The disease subtypes were systemic 8, polyarticular 25 (12 rheumatoid factor positive), oligoarticular 14, enthesitis related arthritis 5, and unclassified 4. Thirty-one patients were switched to SC MTX, 13 of whom had not improved, and 18 who had improved, but had nausea (11) or insufficient clinical improvement (7). After 3 months of SC MTX treatment, 76% of patients were classified as improved and 23% as not improved. Toxicity on SC MTX was less than on oral MTX. CONCLUSION: Our results suggest that for patients failing oral MTX either because of inefficacy or toxicity, the use of SC MTX has a high likelihood of success with more than 70% of patients achieving clinically significant improvement, without clinically significant toxicity

3. ARGYROPOULOU MI, KIORTSIS DN, DASKAS N, XYDIS V, MAVRIDIS A, EFREMIDIS SC, SIAMOPOULOU A: Distensibility and pulse wave velocity of the thoracic aorta in patients with juvenile idiopathic arthritis: an MRI study. Clin Exp Rheumatol 21:6 794-797, 2003
   Organism: Department of Radiology, Medical School, University of Ioannina, 45110 Ioannina, Greece margyrop@ccuoigrFAU - Argyropoulou, M I
   Abstract: OBJECTIVE: An increased incidence of cardiovascular disease has been found in rheumatic disorders. Changes in the variables of aortic elasticity in patients with juvenile idiopathic arthritis (JIA) were evaluated and their relationship to inflammation, anti-rheumatic drugs and traditional cardiovascular risk factors were investigated in this study. METHODS: Phase contrast MR was performed in 31 patients with JIA and 28 age and sex matched controls to evaluate the aortic distensibility and pulse wave velocity (PWV). Disease activity variables, plasma lipid profile, homocysteine, thyroid hormones, glucose and insulin were assessed in the patients. RESULTS: Eighteen patients had oligoarticular, 6 polyarticular and 7 systemic disease. Distensibility was lower (mean: 10.25; SD: 4.18) and PWV was higher (mean: 3.68; SD: 1.59) in the patients compared to the controls (mean: 13.4; SD: 4.99), (mean: 1.38; SD: 0.54) respectively (p < 0.01). A positive correlation between PWV and age was observed in the patients (rs = 0.47, p < 0.01) and controls (rs = 0.72, p < 0.01), and a negative correlation between distensibility and age in the patients (rs = -0.59, p < 0.01) and controls (rs = -0.63, p < 0.01). No statistically significant correlations were found between distensibility and PWV and metabolic and disease activity parameters. When distensibility and PWV were adjusted for age no significant differences were found between the three subtypes of JIA. CONCLUSION: JIA is associated with increased aortic stiffness that might suggest subclinical atherosclerosis. Early detection and follow-up by non-invasive methods may be useful in the prevention of future cardiovascular disease

4. AXFORD JS, CUNNANE G, FITZGERALD O, BLAND JM, BRESNIHAN B, FREARS ER: Rheumatic disease differentiation using immunoglobulin G sugar printing by high density electrophoresis. J Rheumatol 30:12 2540-2546, 2003
   Organism: Academic Unit of Musculoskeletal Disease and Department of Public Health Sciences, St George's Hospital Medical School, Cranmer Terrace, London SW17 0RE, England, UK jaxford@sghmsacukFAU - Axford, John S
   Abstract: OBJECTIVE: To determine whether immunoglobulin G (IgG) sugar printing using high density electrophoresis can be a diagnostic and prognostic test to rapidly differentiate early rheumatoid arthritis (ERA), rheumatoid arthritis (RA), and other rheumatic diseases from each other. METHODS: One hundred fifty-three patients with ERA/RA, psoriatic arthritis (PsA), early psoriatic arthritis (EPsA) ankylosing spondylitis (AS), systemic lupus erythematosus (SLE), juvenile idiopathic arthritis (JIA), early undifferentiated seronegative arthritis (UA), and osteoarthritis (OA) were investigated. Samples of their serum IgG were purified, and sugars were released enzymatically and fluorophore-labelled, then subjected to high density electrophoresis, and relative quantities of each sugar were determined by optical density. RESULTS: Sugar prints of 9 sugars were compiled for each of the 9 disease groups. Specific disease-associated sugar changes were determined by comparison with OA. For example, agalactosylated structures were increased in ERA/RA and EPsA/PsA (p = 0.0001-0.004) and digalactosylated structures were decreased in PsA, AS, and JIA (p = 0.0001-0.04). When the disease groups were compared, each disease was characterized by a unique sugar print comprising 7 of the 9 sugars (p = 0.001-0.005); only g0fb and a1f were not associated. ERA/RA differed in the quantities of monogalactosyl and sialylated sugars (p = 0.006-0.007). The presence of agalactosyl sugars enabled correct prediction of RA in 71.2% of individuals, with a specificity of 84.2% and sensitivity of 50.0%. The area under the sensitivity versus specificity curve was 0.7812. CONCLUSION: IgG sugar printing was found to be effective in differentiation of rheumatic diseases and can differentiate ERA and RA from each other and from other rheumatic diseases; and hence may constitute a relatively rapid diagnostic and prognostic test for patients presenting with arthritis

5. BERNTSON L, GARE BA, FASTH ANDERS, HERLIN T, KRISTINSSON J, LAHDENNE P, MARHAUG GUDMUND, NIELSEN S, PELKONEN P, RYGG M: Incidence of juvenile idiopathic arthritis in the Nordic countries. A population based study with special reference to the validity of the ILAR and EULAR criteria. Rinsho Ganka 30:10 2275-2282, 2003
   Abstract: Objective: To find the incidence of juvenile arthritis according to the ILAR and EULAR criteria within defined areas in the Nordic countries, and to study the validity of the ILAR and EULAR criteria from this perspective. Method: A longitudinal, prospective, population based study with patients enrolled according to the ILAR and EULAR criteria. Twenty doctors in Iceland, Norway, Sweden, Denmark, and Finland collected data from the incidence cases within their catchment areas over a period of 1.5 years, beginning July 1, 1997. Clinical and serological data from the first year of the disease were collected. Results: In the whole group of 315 patients, the incidence rate was 15 per 100,000 children/year (95% CI 13-17) according to the ILAR criteria, varying from 7 (1-13) in Iceland, 19 (7-31) and 23 (10-36) from 2 different regions in Norway, and 9 (5-12) and 16 (9-23) from 2 different areas in Denmark, to 15 (12-18) in Sweden and 21/100,000/year (15-26) in the Helsinki region in Finland. An early peak in distribution for age of onset was found in girls but not in boys. The number of antinuclear antibody (ANA) positive children in the whole group, made up of children who had undergone at least one analyzed ANA test, was 123/315 (39%). Girls were ANA positive in 83/197 (42%) and boys in 40/118 (34%). Uveitis developed in 27/315 (8.6%) children during the first 6 months of the disease. Conclusion: Incidence rates of juvenile arthritis for areas within the Nordic countries were in accord with previous data. The ILAR criteria present slightly higher incidence rates, with a shorter disease duration for inclusion, compared to the EULAR criteria. Patients in one subgroup in either of the criteria sets do not necessarily belong to the expected subgroup in the other set of criteria; e.g., for juvenile ankylosing spondylitis (EULAR) and enthesitis related arthritis (ILAR). Our epidemiological findings are a reminder to be aware of possible new subgroups in children with juvenile arthritis

6. BURNHAM JM, LEONARD MB: Bone disease in pediatric rheumatologic disorders. Curr Rheumatol Rep 6:1 70-78, 2004
   Organism: Department of Pediatrics, The Children's Hospital of Philadelphia, 34th Street and Civic Center Boulevard, CHOP North, Room 1564, Philadelphia, PA 19104, USA leonard@emailchopeduFAU - Burnham, Jon M
   Abstract: Children with rheumatic disorders have multiple risk factors for impaired bone health, including delayed growth and development, malnutrition, decreased weight-bearing activity, inflammation, and glucocorticoid therapy. The impact of rheumatic disease during childhood may be immediate, resulting in fragility fractures, or delayed, because of suboptimal peak bone mass accrual. Recent years have seen increased interest in the effects of pediatric rheumatic disorders on bone mineralization, such as juvenile rheumatoid arthritis, systemic lupus erythematosus, and juvenile dermatomyositis. This review outlines the expected gains in bone size and mass during childhood and adolescence, and summarizes the advantages and disadvantages of available technologies for the assessment of skeletal growth and fragility in children. The varied threats to bone health in pediatric rheumatic disorders are reviewed, with emphasis on recent insights into the molecular mechanisms of inflammation-induced bone resorption. The literature assessing bone deficits and risk factors for impaired bone health in pediatric rheumatic disorders is reviewed, with consideration of the strengths and limitations of prior studies. Finally, future research directions are proposed

7. DASS R, SINGH S, KUMAR V, VAIPHEI K, AGRAWAL S, SAEED T, MINZ RW: Varicella glomerulonephritis mimicking microscopic polyangiitis. Rheumatol Int .: 2004
   Organism: Advanced Pediatric Center, Department of Pediatrics, Postgraduate Institute of Medical Education and Research, Chandigarh, India 160012
   Abstract: Varicella in childhood is usually a self-limiting illness with few complications. Varicella nephritis is an uncommon entity and seen mostly in immunocompromized individuals. We report a 14-year-old boy with juvenile rheumatoid arthritis who developed varicella nephritis and in whom the renal manifestations preceded the skin lesions by 1 week. This is an extremely unusual occurrence, and only one case has been described before. Such a presentation can mimic the clinical features of microscopic polyangiitis

8. FOELL D, FROSCH M, SCHULZE ZUR WA, VOGL T, SORG C, ROTH J: Methotrexate treatment in juvenile idiopathic arthritis: when is the right time to stop? Ann Rheum Dis 63:2 206-208, 2004
   Organism: Department of Paediatrics, University of Muenster, Albert-Schweitzer-Str 33, D-48149 Muenster, Germany Institute of Experimental Dermatology, University of Muenster, Von-Esmarch-Str 58, D-48149 Muenster, GermanyFAU - Foell, D
   Abstract: OBJECTIVES: To investigate whether prolonged methotrexate (MTX) treatment after induction of remission influences the subsequent duration of remission in patients with juvenile idiopathic arthritis (JIA), and to analyse the usefulness of myeloid related proteins 8 and 14 (MRP8/MRP14) as predictive markers for the stability of remission at the time when MTX is withdrawn. METHODS: Twenty five patients with oligoarticular and polyarticular JIA who received MTX to induce remission were followed up. MTX treatment was stopped after a mean of 3.8 months (group 1) or 12.6 months (group 2) after remission was documented. Differences in the number of relapses between these groups were looked for. Additionally, MRP8/MRP14 were analysed by ELISA in 22 patients. RESULTS: No difference was found in the number of relapses between patients with prolonged or early discontinued MTX treatment. Patients who were in stable remission had significantly lower MRP levels when MTX was discontinued than patients with relapses. With a cut off point for MRP8/MRP14 at 250 ng/ml, sensitivity and specificity were 100% and 70%, respectively. CONCLUSION: Longer duration of MTX treatment after induction of remission does not generally improve the status of remission in patients with JIA. Residual synovial inflammation seems to influence the rate of relapses after discontinuation of MTX treatment. MRP8/MRP14 indicate residual activity even in the absence of other laboratory or clinical signs of continuing inflammation. Normal serum concentrations of MRP8/MRP14 in clinical inactive arthritis may help to identify patients in whom MTX can be safely withdrawn after remission is achieved

9. FREED GL, JEE S, STEIN L, SPERA L, CLARK SJ: Comparing the self-reported referral and management preferences of pediatricians and family physicians for children with juvenile rheumatoid arthritis. J Rheumatol 30:12 2700-2704, 2003
   Organism: Child Health Evaluation and Research (CHEAR) Unit, Division of General Pediatrics, University of Michigan, 300 NIB 6E08, Ann Arbor, MI 48109-0456, USA gfreed@medumicheduFAU - Freed, Gary L
   Abstract: OBJECTIVE: The symptoms of juvenile rheumatoid arthritis (JRA) are often first recognized by primary care physicians. Little is known about the determinants of the initial management and referral patterns of these physicians for children with JRA. We compared the self-reported preferences and practices of pediatricians (PD) and family physicians (FP) in the diagnosis and management of children with JRA. METHODS: Surveys were mailed to a national random sample of 700 PD and 867 FP. Questions included prior experience with JRA, usual patterns in the diagnosis and management of JRA, perception of the need for guidelines for referral and management of this condition, and physician demographic information. Data analysis included univariate and bivariate analysis. RESULTS: Response rates were 69% for PD and 49% for FP. Most respondents had seen very few JRA cases in the previous 5 years. Only 1% of respondents reported that they provided all diagnosis and management for patients with JRA. Forty-two percent of PD and 32% of FP refer all JRA diagnosis and management to subspecialists, while 46% of PD and 61% of FP refer only to confirm the diagnosis and guide initial therapy (p = 0.011). More PD than FP (PD 92% vs FP 76%; p = 0.001) referred patients with JRA to pediatric rheumatologists, while more FP than PD referred to general rheumatologists (PD 17% vs FP 37%; p = 0.001). The majority of FP reported feeling more comfortable managing rheumatologic disease in adults than children (82%). Few respondents felt that they were up to date on the latest advances in JRA treatment (PD 10% vs FP 4%; p = 0.024). CONCLUSION: Multiple factors may contribute to physicians' referral practice, including a patient's clinical status and the physician's beliefs of inadequacy of training and inability to stay up to date. The pattern of care that children with JRA receive likely will be influenced by initial presentation to a PD or to a FP

10. GAO JS, WU H, TIAN J: [Treatment of patients with juvenile rheumatoid arthritis with combination of leflunomide and methotrexate]. Zhonghua Er Ke Za Zhi 41:6 435-438, 2003
    Organism: Department of Rheumatism and Immunology, Second Xiangya Hospital, Central South University, Changsha 410011, ChinaFAU - Gao, Jie-Sheng
    Abstract: OBJECTIVE: To evaluate the efficacy and safety of the combined therapy with leflunomide and methotrexate in the patients with juvenile rheumatoid arthritis (JRA). METHODS: Forty patients with active polyarthritis JRA were divided into 2 groups. Group 1 (n = 21) received leflunomide tablet (1 mg/(kg.day) on days 1 - 3; then [(0.2 - 0.4) mg/kg per day] plus methotrexate (0.3 mg/kg i.v. every two weeks till clinical remission, then oral tablet 0.2 mg/kg weekly). Group 2 received the same doses of methotrexate in the same way. Permitted concomitant drugs included stable doses of NSAIDs and a low dose of prednisone during the course of treatments. The clinical assessments included the number of tender and swollen joints, tender articular index, swollen articular index, general articular function score, parents and physician's evaluation score, erythrocyte sedimentation rate, serum C-reactive protein and rheumatoid factor. Drug safety was assessed by observing the reaction of mucous membrane, skin, gastrointestinal tract, nervous system, hematologic changes, liver and renal function. Statistical comparison between two groups was performed by using analysis of variance, t test and chi(2) test. RESULTS: Efficacy and safety was assessed at 12th and 26th week. Average improvement rate of leflunomide plus methotrexate group at 12th week and 26th week was respectively 39.6% and 71.9%; while that of control group was 27.5% and 49.5%, i.e., there was significant difference between the two groups (P < 0.01). Average remission rate of leflunomide plus methotrexate group at 12th week and 26th week was respectively 4.76% and 38.10%; while that of control group (methotrexate only) was respectively 0, 0. The clinical improvement in the group treated with leflunomide plus methotrexate was significantly greater than control group (P < 0.01). There was no significant difference (9.5% v 5.3%) in occurrence rate of side effects between the two groups. Side effects included leucocytopenia and raised aminotransferase. They were mostly mild and tolerable. CONCLUSION: The effect of the leflunomide and methotrexate therapy in patients with active JRA was better than methotrexate alone. The combination therapy with leflunomide and methotrexate was safe and well tolerated

11. JAWAD AS: Systemic juvenile idiopathic arthritis, Kikuchi's disease and haemophagocytic lymphohistiocytosis. Rheumatology (Oxford) 43:2 254, 2004

12. JUAREZ OH, FLORES PJ, LARES A, I, LOREDO AA, CARBAJAL RL: Comparative pharmacokinetics of acetyl salicylic acid and its metabolites in children suffering from autoimmune diseases. Biopharm Drug Dispos 25:1 1-7, 2004
    Organism: Laboratorio de Farmacologia, Instituto Nacional de Pediatria (INP), MexicoFAU - Juarez Olguin, Hugo
    Abstract: The aim of the present study was to compare the effect produced by juvenile rheumatoid arthritis (JRA) or rheumatic fever (RF) on the pharmacokinetics of acetyl salicylic acid (ASA) and its metabolites in children with autoimmune diseases (AD). Methods-A prospective, open labelled study was performed in 17 children with JRA and 17 with RF who received a single dose of 25 mg ASA/kg orally. The pharmacokinetics of ASA and its metabolites were determined. The blood and urine levels of each salicylate collected during 24 h were measured by HPLC. A group of 15 healthy teenage volunteers was included as a control group. Results-The maximum plasma concentration, half-life time, area under the curve and the amount of salicylates excreted were statistically different between the JRA and the RF groups, as well as between the RF group and the controls, however, there were no significant differences between the JRA group and the controls. Conclusions-Dosage schemes must be adjusted for JRA patients, since the half life in these patients is longer than in RF patients. However, due to ample variability of pharmacokinetic parameters it is recommended that dose schemes are individualized on the type of autoimmune disease considered

13. KISHIMOTO T, HAMAZAKI T, YASUI M, SASABE M, OKAMURA T, SAKATA N, INOUE M, YAGI K, KAWA K: Autologous hematopoietic stem cell transplantation for 3 patients with severe juvenile rheumatoid arthritis. Int J Hematol 78:5 453-456, 2003
    Organism: Department of Pediatrics, Osaka Medical Center and Research Institute for Maternal and Child Health, Izumi City, Osaka, JapanFAU - Kishimoto, Tomoko
    Abstract: We performed autologous CD34+ stem cell transplantation in 3 patients with juvenile rheumatoid arthritis (JRA) refractory to conventional treatment. All patients had systemic type JRA. In case 1 (a 3-year-old boy), purified CD34+ cells from bone marrow were transplanted after a preconditioning regimen consisting of cyclophosphamide (200 mg/kg) and antithymocyte globulin (ATG) (40 mg/kg). However, the disease flared soon after transplantation. In case 2 (a 13-year-old girl) and case 3 (a 21-year-old woman), a preconditioning regimen consisting of etoposide (VP16) (2 g/m2), thiotepa (300 mg/m2), and ATG (40 mg/kg) was followed by transplantation of purified CD34+ stem cells harvested from peripheral blood mononuclear cells. The patients in cases 2 and 3 attained complete remission without any medication. Thus for patients with refractory JRA, autologous CD34+ cell transplantation appears to be a safe and feasible choice of treatment in terms of good quality of life. However, a greater number of patients and a longer observation period are needed before definitive conclusions can be drawn

14. KOVACS L, HLAVATA A, SMOLENOVA J, CHANDOGA J, PAVLOVICOVA E: Syndromes of Periodic Fever - The Syndrome of Mevalonic Aciduria and Hyperimmunoglobulinemia D
    SYNDROMY PERIODICKEJ HORUCKY - SYNDROM MEVALONOVEJ ACIDURIE A HYPERIMUNOGLOBULINEMIE D. Cesko-Slovenska Pediatrie (Czech Republic ) 58:12 744-749, 2003
    Abstract: Periodic fever is defined as recurrences of fever that last from a few days to a few weeks, separated by symptom-free intervals of variable duration. This pattern of fever can be caused by recurrent infections or neoplastic disorders but also by noninfectious inflammatory disorders. It is important to review the medical history carefully in patients with recurrent febrile attacks. Patients with periodic fever that persists for more than two years rarely have infections of malignant disorders. Attacks with a predictable course and a similar set of symptoms, along with a family history of such attacks, may suggest the presence of a noninfectious form of periodic fever. Although numerous disorders, such as juvenile rheumatoid arthritis, Still's disease and, Crohn's disease, can cause periodic fever, this article will focus on hereditary periodic fever syndromes. The authors present two cases of the mevalonic aciduria/hyper IgD syndrome of various severity. For differential diagnostic reasons they also draw attention to other, etiologically diverse types of hereditary fever syndromes, such as familial Mediterranean fever, the tumor necrosis factor (TNF) receptor-associated periodic syndrome, the Muckle-Wells syndrome and the familial cold autoinflammatory syndrome

15. LEONE V, PRESANI G, PERTICARARI S, TOMMASINI ALBERTO, CROVELLA S, LENHARDT A, PICCO P, LEPORE LOREDANA_(REPRINT): Chronic infantile neurological cutaneous articular syndrome: CD10 over-expression in neutrophils is a possible key to the pathogenesis of the disease. European Journal Of Pediatrics 162:10 669-673, 2003
    Abstract: Chronic, Infantile, Neurological, Cutaneous and Articular Syndrome (CINCA) or Neonatal/Infantile Onset Multisystem Inflammatory Disease (NOMID/IOMID) is a rare, multisystem inflammatory disease characterised by neonatal onset of urticarial symptoms, persistent rash, ocular inflammatory lesions, progressive articular and neurological involvement and associated with characteristic overgrowth of the ossification nucleus of the patella. The tissues involved are extensively infiltrated by inflammatory cells, mostly neutrophils. This paper describes the clinical features of three new cases as well as a study of activation markers in neutrophils and search for mutations of the CIAS1gene in these patients. Clinical records of three cases of CINCA are reported. For genetic analysis, exon 3 of the CIAS1gene was amplified and sequenced. Immunophenotype, oxidative burst and phagocytosis were analysed in neutrophils obtained from all the three CINCA patients as well as from eight juvenile idiopathic arthritis (JIA) patients and eight healthy controls. Functional assays in neutrophils were normal in all three patients with CINCA syndrome and did not differ from those of JIA patients and healthy controls. The surface density of CD10 was significantly higher on neutrophils from CINCA patients as compared to those of JIA and controls (P<0.0005). In one subject a new missense mutation in the CIAS1gene was identified. Conclusion: The hyper expression of the activation antigen CD10/NEP in neutrophils from these three cases of CINCA, as compared to JIA patients and healthy controls, irrespective of the presence of mutations in CIAS1, could be a marker of the inflammatory disorder typical of some patients with CINCA syndrome

16. LI CW, HU J, PI SH: [Clinical characteristics of children with enthesitis related arthritis]. Zhonghua Er Ke Za Zhi 41:11 835-838, 2003
    Organism: Group of Rheumatology and Immunology, Department of Internal Medicine, Tianjin Children's Hospital, Tianjin 300074, ChinaFAU - Li, Chong-Wei
    Abstract: OBJECTIVE: To study clinical characteristics of children with enthesitis related arthritis (ERA). METHODS: Twelve patients fulfilling the international league of associations for rheumatolgy (ILAR) criteria for classification of juvenile idiopathic arthritis (JIA) and ERA were referred to our department between August and November, 2002. Their gender, age, family history, clinical manifestations, imaging data, laboratory data and treatment regimens were analyzed retrospectively. RESULTS: Of the 12 patients, 11 were male, only one was female; their age ranged from 4 to 16 years, and the median age was 10.5 years. Ten (83%) of the patients were older than eight years. Among their first degree relatives, one had definite ankylosing spondylitis (AS), and 3 presented with a history of inflammatory low back pain. Enthesitis occurred in 9. Synovitis occurred in 11, most of which were oligoarthritis, predominantly affecting large joints of the lower limbs in an asymmetric pattern. Seven patients underwent CT scan, and only one had erosions of the sacroiliac joints to achieve a diagnosis of juvenile AS. Ten had fever at the onset, and one had a history of diarrhea preceding the symptoms of arthritis. Urethritis and balanitis circinata occurred in 3 cases fulfilling the classification criteria of Reiter's syndrome, with conjunctivitis in 2 and corneitis in one. Elevated inflammatory indicators such as white blood cell, neutrophil, platelet, erythrocyte sedimentation rate, C-reactive protein, immunoglobulins and serum complement C3 were common during the acute illness. Mild anemia was found in 4, and reactive hemophagocytosis in 4 bone marrow specimens. DNA of human parvovirus B19 was detected in sera of 2 cases. One had positive IgM antibody to coxsackie virus B. All 12 cases were rheumatoid factor negative and HLA-B27 positive. Nonsteroidal anti-inflammatory drugs and sulfasalazine were the mainstay of treatment. Corticosteroids were added in 3 cases as a "bridge" therapy due to the severe systemic inflammation. Methotrexate was used in 4 cases with refractory disease or with the hip involved, and in 2 of them cyclophosphamide was added. CONCLUSION: The clinical characteristics of ERA can facilitate an early diagnosis so as to avoid joint damage and disabilities

17. MARIK I, MARIKOVA O, ZEMKOVA D, KUKLIK M, KOZLOWSKI K: Dominantly inherited progressive pseudorheumatoid dysplasia with hypoplastic toes. Skeletal Radiol .: 2004
    Organism: Ambulant Centre for Defects of the Locomotor Apparatus, Prague, Czech Republic
    Abstract: OBJECTIVE. To present four related patients with progressive pseudorheumatoid dysplasia (PPsRD) each with distinctive history, unique phenotype and some peculiar radiographic findings. RESULTS AND CONCLUSIONS. The history was characterised by weather-dependent articular pain. The unique phenotypic features were hypoplasia/dysplasia of one or two toes. Peculiar radiographic findings were hypoplasia of the 3rd and 4th metatarsals, platyspondyly with rectangular shape of the lumbar spinal canal, progressive narrowing of the joint spaces and early synovial chondromatosis. Finally, the condition was inherited as a dominant trait. This constellation of abnormalities constitutes a distinct form of PPsRD. PPsRD must be differentiated from other bone dysplasias, specifically spondyloepiphyseal dysplasias, autosomal dominant spondylarthropathy, juvenile rheumatoid arthritis and osteoarthritis

18. MARTINI G, TREGNAGHI A, BORDIN T, VISENTIN MT, ZULIAN F: Rice bodies imaging in juvenile idiopathic arthritis. J Rheumatol 30:12 2720-2721, 2003
    Organism: Rheumatology Unit, Department of Pediatrics, University of Padua, Padua, Italy martini@pediatriaunipditFAU - Martini, Giorgia

19. MOHR W: Synovial haemangioma
    <ORIGINAL> Synoviales Haemangiom. Aktuelle Rheumatologie 28:4 225-227, 2003
    Abstract: Synovial haemangiomas are rare tumours which preferentially occur in the knee joint of younger patients. A history of pain is the most frequent symptom, joint swelling and enlargement are common, limitation of motion may occur. In the case report the morphology of the synovial membrane of an 11 year-old girl, clinically diagnosed as juvenile chronic arthritis, is described. The characteristic findings are severe synovial siderosis and synovial villi with ectatic or cavernous blood vessels. Synovectomy is regarded as the treatment of choice, recurrences of the tumour may occur

20. OZEN S, BAKKALOGLU A, YILMAZ E, DUZOVA ALI, BALCI B, TOPALOGLU R, BESBAS N: Mutations in the gene for familial Mediterranean fever: Do they predispose to inflammation? Rinsho Ganka 30:9 2014-2018, 2003
    Abstract: Objective: To analyze 70 individuals who were found to have the Mediterranean fever (MEFV) gene for the presence of definite familial Mediterranean fever (FMF) and to assess if they were prone to clinical and laboratory inflammation. We also prospectively evaluated 72 patients with childhood rheumatic diseases for the presence of MEFV mutations. Methods: Seventy patients with one MEFV gene mutation were reevaluated for the presence of a clinical FMF phenotype using a new set of criteria. They were also questioned for the presence of musculoskeletal symptoms and rheumatic diseases. They were sampled for erythrocyte sedimentation rates and C-reactive protein levels. A second group with childhood rheumatic diseases were diagnosed according to international criteria. Results: Median age of the 70 heterozygous individuals was 12 years. About 1/3 (34.3%) were classified with clinical FMF phenotype according to the suggested criteria. Fifteen (21.4%) were classified as normal and 3 (4.3%) had recurrent abdominal pains but did not fulfill all criteria for clinical FMF. Overall, 28 (40.0%) had some form of rheumatic complaint and 15 (21.4%) had developed a rheumatic disease including Behcet's disease, a vasculitis, or acute rheumatic fever. The mean ESR and CRP levels were 45.47+-33.05 mm/h and 4.00+-6.73 mg/dl, respectively. Among the 72 patients with rheumatic diseases of childhood, 22 (30.5%) carried one or 2 mutations of the MEFV gene. The mutated allele frequency among patients with rheumatic diseases was significantly higher than those in controls (p<0.05). Within this group, among the 59 patients with juvenile idiopathic arthritis 15 had mutations in the heterozygous or homozygous form. Conclusion: We confirm the acute phase response in the carriers for MEFV mutations. We suggest that these patients may have a tendency to develop certain manifestations due to an increased baseline of inflammation, and the presence of these mutations may affect their disease course when they develop rheumatic disease

21. PALERMO TM, VALENZUELA D, STORK PP: A randomized trial of electronic versus paper pain diaries in children: impact on compliance, accuracy, and acceptability. Pain 107:3 213-219, 2004
    Organism: Department of Pediatrics, Division of Behavioral Pediatrics and Psychology, Rainbow Babies and Children's Hospital, 11100 Euclid Avenue, 44106, Cleveland, OH, USAFAU - Palermo, Tonya M
    Abstract: Electronic diary assessment of pain and disability has become increasingly popular in adult chronic pain research but use of this methodology with children has received limited attention. The aim of this study was to compare two formats of a prospective daily diary (handheld computer=e-diary; paper diary=p-diary) on children's compliance, accuracy, and acceptability ratings. Sixty children, ages 8-16 (M=12.3) with headaches or juvenile idiopathic arthritis, were randomized to receive either e-diaries administered via home visits (n=30) or p-diaries (n=30) handed out during clinic visits for return by mail. Results demonstrated significant mean differences in diary entries completed between groups, with children with e-diaries completing more days (M=6.6) compared to children with p-diaries (M=3.8), P<0.001. Diaries returned by children in the p-diary group contained significantly more errors and omissions compared to diaries returned by children in the e-diary group (which contained none), P<0.001. Children rated both diary formats as highly acceptable and easy to use. A significant genderxdiary format interaction (P<0.01) was found for compliance where boys demonstrated greater compliance with the e-diary format. Findings demonstrated that the e-diary was feasible to use with children and showed significantly greater compliance and accuracy in diary recording compared to traditional paper diaries in a population of children with recurrent pain

22. RYDHOLM U: Nonprosthetic Surgery of the Juvenile Idiopathic Arthritic Hip. Techniques in Orthopaedics (United States ) 18:3 272-278, 2003
    Abstract: Control of hip disease is very important for maintaining mobility and independence in patients with juvenile idiopathic arthritis (JIA). Hip deformity and pain must be treated early by drugs and physiotherapy and, if necessary, by arthroscopic joint lavage and corticosteroids. Core decompression is a minor procedure that can provide considerable relief from aching pain. Soft tissue releases as well as intertrochanteric osteotomy can affect the loading situation of the whole lower extremity, and also give the possibility of regeneration of cartilage in children with clinical deformities and radiographic growth disturbances of the hip. Minor surgical procedures should always be considered if they can delay the requirement for total joint replacement

23. SCHMELING H, SELIGER E, HORNEFF G: Growth reconstitution in juvenile idiopathic arthritis treated with etanercept. Clin Exp Rheumatol 21:6 779-784, 2003
    Organism: Department of Pediatrics, Martin-Luther University Halle-Wittenberg, Halle, GermanyFAU - Schmeling, H
    Abstract: OBJECTIVE: Growth failure is a leading problem in uncontrolled juvenile idiopathic arthritis. It also affects 10% of patients who are not treated with corticosteroids. The influence of proinflammatory cytokines like interleukin-1 beta, interleukin-6 and tumour necrosis factor on the neuroendocrine axis as well as on the production of insulin-like growth factors (IGFs) has been postulated. The objective of the current study was to evaluate effects of highly active antirheumatic treatment with tumour necrosis factor antagonist on growth retardation. Seven out of 18 patients with refractory juvenile idiopathic arthritis treated with etanercept demonstrated growth retardation leading to short stature. METHODS: Antropometric measurements and disease activity parameters--including the number of swollen and tender joints, morning stiffness, ESR and CRP levels--were monitored monthly during the first year of treatment and every 3 months thereafter. Serum levels of IGF-1 and IFG-BP were measured as well. RESULTS: Upon treatment with etanercept, growth velocity increased from 3.7 +/- 1.2 cm before the beginning of the therapy to 7.6 +/- 1.2 cm in the first year of treatment (p < 0.001). The average length-standard-deviation-score (SDS) increased from -2.4 +/- 1.0 to -1.9 +/- 0.9 after one year and to -1.1 +/- 0.9 after two years (p = 0.05) indicating catch-up growth. Prior to the therapy, serum levels of insulin-like growth factor-1 and of insulin-like growth factor binding protein-3 were within the normal range but increased significantly upon treatment (p < 0.001). An inverse correlation of the IGF-1 serum level to CRP was found. CONCLUSIONS: An intensified anti-inflammatory treatment using etanercept has a beneficial effect on growth in children with a so far uncontrolled inflammatory disease. This effect might be related to the cessation of the inhibitory effect of proinflammatory cytokines on the synthesis of IGF-1 and IGF-BP-3 in the liver. Growth failure should be included in the evaluation of antirheumatic treatment

24. THE GROUP OF IMMUNOLOGY SOCIETY OF PEDIATRICS CHINESE MEDICAL ASSOCIATION: [National investigation program of systemic onset juvenile idiopathic arthritis in diagnosis, therapy and prognosis]. Zhonghua Er Ke Za Zhi 41:6 415-416, 2003

25. VAN RIJN RR, GROOTFAAM DS, LEQUIN MH, BOOT AM, VAN BEEK RD, HOP WC, VAN KUIJK C: Digital Radiogrammetry of the Hand in a pediatric and Adolescent Dutch Caucasian Population: Normative Data and Measurements in Children with Inflammatory Bowel Disease and Juvenile Chronic Arthritis. Calcif Tissue Int .: 2004
    Organism: Department of Radiology, Academic Medical Centre/Emma Children's Hospital, Amsterdam, The Netherlands
    Abstract: We have evaluated the applicability of a new Digital X-ray Radiogrammetry (DXR) system in a Dutch Caucasian pediatric population. For this study we enrolled 535 healthy participants who all signed an informed consent form. In addition, 20 children suffering from inflammatory bowel disease (IBD) and juvenile chronic arthritis (JCA) were enrolled. Radiographs of the left hand were obtained from all participants. From the healthy population a subset of children with a history of forearm fractures were separately analyzed. Measurements consisted of DXR (X-posure((R)); Pronosco-Sectra, Linkoping, Sweden). Five hundred thirty-five subjects were enrolled in the study. Twenty-two subjects (4.3%) were discontinued (age 3-10 years), all because of a nonrecognizable radiograph by the DXR system. The short-term coefficient of variation of DXR in this population was 0.59%. Significant differences in DXR-BMD between boys and girls for the ages of 11, 12, 16, 17, and 18 years were found. There were also significant differences in DXR-BMD between the sequential Tanner stages. For 88 subjects repeat radiographs were available (mean interval 1.8 years). In all cases an increase in DXR-BMD was seen Girls with IBD, JCA, or a history of forearm fractures and boys with IBD showed a significantly lower DXR-BMD compared with healthy controls. We show that DXR is an applicable technique in children. Also, in a small subpopulation it is possible to discriminate children with a high risk of low BMD

26. WAKHLU A, GUPTA D, AGGARWAL A, MISRA R: Low levels of anti-histone antibodies in north Indian children with juvenile rheumatoid arthritis. Indian J Med Res 118:204-7.: 204-207, 2003
    Organism: Department of Immunology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, IndiaFAU - Wakhlu, A
    Abstract: BACKGROUND & OBJECTIVES: Early onset pauciarticular disease with uveitis is distinctly uncommon in Indian children with juvenile rheumatoid arthritis (JRA). The occurrence of anti-histone antibodies (AHA) in serum is strongly associated with presence of uveitis. There is a paucity of information from India on the levels of AHA in patients of JRA. In this study, an attempt was made to evaluate the levels of IgG and IgM antibodies to histones in children with JRA in north India. METHODS: Serum samples of 148 children with JRA (84 boys, 64 girls) were collected. Clinical details including onset, symptoms and course of the disease in each patient were recorded. Detailed eye examination including slit lamp examination was done in all patients at presentation and yearly thereafter to rule out uveitis. The presence of antihistone IgG and IgM antibodies was studied by ELISA. Antinuclear antibodies (ANA) were measured by indirect immunofluorescence using HEP-2 cells as substrate at a screening dilution of 1:40. RESULTS: Of the 148 children, 54 had pauciarticular (12 early onset and 42 late onset), 64 polyarticular and 30 systemic onset disease respectively. ANA were present in two children. AHA were raised in 15 (10%) children, of whom 10 had IgM antibodies, 3 had IgG and 2 had both isotypes. None of the children with early onset pauciarticular disease had uveitis, ANA or AHA. INTERPRETATION & CONCLUSION: The low occurrence of AHA and uveitis in our subset of patients with JRA is in contrast to that reported from Western countries. The low occurrence is unlikely due to technical reasons as the antigen that has been used consistently showed significant binding to serum from patients with systemic lupus erythematosus (SLE). This is in accordance with the rarity of early onset pauciarticular disease and chronic uveitis in these patients. More studies from other parts of the country are required to validate this observation

27. WAKHLU A, GUPTA D, AGGARWAL A, MISRA R: Low levels of anti-histone antibodies in north Indian children with juvenile rheumatoid arthritis. Indian Journal of Medical Research (India ) 118:NOV. 204-207, 2003
    Abstract: Background & objectives: Early onset pauciarticular disease with uveitis is distinctly uncommon in Indian children with juvenile rheumatoid arthritis (JRA). The occurrence of anti-histone antibodies (AHA) in serum is strongly associated with presence of uveitis. There is a paucity of information from India on the levels of AHA in patients of JRA. In this study, an attempt was made to evaluate the levels of IgG and IgM antibodies to histones in children with JRA in north India. Methods: Serum samples of 148 children with JRA (84 boys, 64 girls) were collected. Clinical details including onset, symptoms and course of the disease in each patient were recorded. Detailed eye examination including slit lamp examination was done in all patients at presentation and yearly thereafter to rule out uveitis. The presence of antihistone IgG and IgM antibodies was studied by ELISA. Antinuclear antibodies (ANA) were measured by indirect immunofluorescence using HEP-2 cells as substrate at a screening dilution of 1:40. Results: Of the 148 children, 54 had pauciarticular (12 early onset and 42 late onset), 64 polyarticular and 30 systemic onset disease respectively. ANA were present in two children. AHA were raised in 15 (10%) children, of whom 10 had IgM antibodies, 3 had IgG and 2 had both isotypes. None of the children with early onset pauciarticular disease had uveitis, ANA or AHA. Interpretation & conclusion: The low occurrence of AHA and uveitis in our subset of patients with JRA is in contrast to that reported from Western countries. The low occurrence is unlikely due to technical reasons as the antigen that has been used consistently showed significant binding to serum from patients with systemic lupus erythematosus (SLE). This is in accordance with the rarity of early onset pauciarticular disease and chronic uveitis in these patients. More studies from other parts of the country are required to validate this observation

28. WOOLF AD, PFLEGER B: Burden of major musculoskeletal conditions. Bull World Health Organ 81:9 646-656, 2003
    Organism: Peninsula Medical School, Duke of Cornwall Department of Rheumatology, Royal Cornwall Hospital, Truro TR1 3LJ, England woolfa@dialinnetFAU - Woolf, Anthony D
    Abstract: Musculoskeletal conditions are a major burden on individuals, health systems, and social care systems, with indirect costs being predominant. This burden has been recognized by the United Nations and WHO, by endorsing the Bone and Joint Decade 2000-2010. This paper describes the burden of four major musculoskeletal conditions: osteoarthritis, rheumatoid arthritis, osteoporosis, and low back pain. Osteoarthritis, which is characterized by loss of joint cartilage that leads to pain and loss of function primarily in the knees and hips, affects 9.6% of men and 18% of women aged > 60 years. Increases in life expectancy and ageing populations are expected to make osteoarthritis the fourth leading cause of disability by the year 2020. Joint replacement surgery, where available, provides effective relief. Rheumatoid arthritis is an inflammatory condition that usually affects multiple joints. It affects 0.3-1.0% of the general population and is more prevalent among women and in developed countries. Persistent inflammation leads to joint destruction, but the disease can be controlled with drugs. The incidence may be on the decline, but the increase in the number of older people in some regions makes it difficult to estimate future prevalence. Osteoporosis, which is characterized by low bone mass and microarchitectural deterioration, is a major risk factor for fractures of the hip, vertebrae, and distal forearm. Hip fracture is the most detrimental fracture, being associated with 20% mortality and 50% permanent loss in function. Low back pain is the most prevalent of musculoskeletal conditions; it affects nearly everyone at some point in time and about 4-33% of the population at any given point. Cultural factors greatly influence the prevalence and prognosis of low back pain

29. WULFFRAAT M, DE K, I, BRINKMAN D, TEN CATE R, DER NET JJ, RIJKERS GT, KUIS W: Autologous stem cell transplantation for refractory juvenile idiopathic arthritis: Current results and perspectives. Transplantation Proceedings 34:7 2925-2926, 2002

30. ZHANG QY, DONG ZY: [Responses of gamma-interferon and interleukin-4 in children with juvenile rheumatoid arthritis]. Zhonghua Er Ke Za Zhi 41:11 857, 2003

31. ZHAO SY, JIANG ZF, REN ZH: [Causes and diagnostic procedure of diffuse lung disease in 28 children]. Zhonghua Er Ke Za Zhi 41:7 542-545, 2003
    Organism: Beijing Children's Hospital Affiliated to Capital University of Medical Sciences, Beijing 100045, ChinaFAU - Zhao, Shun-Ying
    Abstract: OBJECTIVE: Diffuse lung disease comprises a large, heterogeneous group of pulmonary interstitial and parenchymal disease. It is therefore difficult to some extent to make etiologic diagnosis. Little information on clinical spectrum and diagnostic evaluation of pediatric diffuse lung disease is available in our country. The purpose of this study was to explore the causes of and diagnostic approach to diffuse lung disease in children. METHODS: Twenty-eight children with diffuse lung disease aged 2 months to 14 years were studied retrospectively. Their history, physical examination, radiographic findings, final diagnosis and diagnostic processes were reviewed. RESULTS: Confirmed diagnosis was established in 25 cases and suggestive diagnosis in 3 cases. Confirmed diagnoses included: mycoplasma pneumonia in 1 case, Chlamydia trachomatis pneumonia in 2 cases, Epstein-Barr virus pneumonia in 1, CMV pneumonia in 2, hematogenous disseminated pulmonary tuberculosis in 3, pulmonary cryptococcosis in 1, invasive pulmonary aspergillosis in 2, Staphylococcus aureus sepsis in 1, diffuse bronchiectasis in 2, idiopathic pulmonary hemosiderosis in 1, idiopathic pulmonary fibrosis in 1, extrinsic allergic alveolitis in 1, HIV-related lymphocytic interstitial pneumonitis in 1, Wegner's granulomatosis in 1, Langerhan's cell histiocytosis in 2, and lymphoma in 3. Suggestive diagnoses included Nocardia pneumonia in 1, Pneumocystis carinii pneumonia in 1, and juvenile rheumatoid arthritis-associated pulmonary fibrosis in 1. The diagnostic directions of 26 patients were conducted by radiographic features. In 17 of 26 cases, the diagnostic range was confined by history. The diagnosis of 14 cases was made by noninvasive tests including antibody detection, bacterial culture, those of 8 cases by examination of biopsy material, and those of 2 cases by autopsy. CONCLUSIONS: The causes of pediatric diffuse lung disease included pulmonary infectious disease, idiopathic pulmonary disease and pulmonary lesion associated with systemic diseases. The diagnosis may be made by radiography, history, physical examination, noninvasive tests in most cases, while in some cases invasive procedures were necessary