Bibliography September 04

1. ADIB N, OWERS KL, WITT JD, OWENS CM, WOO P, MURRAY KJ: Isolated inflammatory coxitis associated with protrusio acetabuli: a new form of juvenile idiopathic arthritis? Rheumatology (Oxford) .: 1919
   Organism: Departments of Rheumatology, Great Ormond Street Hospital, London, UK
   Abstract: Background. Isolated hip disease in the context of chronic childhood inflammatory arthritis is uncommon. This paper reports 14 children who presented to the rheumatology and orthopaedic departments of our hospitals with severe hip symptoms, and who continued to have primarily hip disease throughout their clinical course. Our aim was to characterize and present the relevant demographic, clinical, investigational, treatment and outcome data from the above cohort. Methods. All paediatric cases with the diagnosis of protrusio acetabuli, Otto pelvis or idiopathic chondrolysis who were seen in the past 15 yr at Great Ormond Hospital and Middlesex Hospital in London were identified and their case notes were searched retrospectively for relevant information. Results. In 11 cases, the disease progressed to involve no joints other than the contralateral hip. None were considered to have a specific subtype of juvenile idiopathic arthritis (JIA) and all tested were negative for HLA-B27. Elevation of serum inflammatory markers was variable. Protrusio acetabuli was the predominant radiological feature. There were definite inflammatory changes on the gadolinium-enhanced magnetic resonance imaging study in all patients who had this procedure performed (seven cases). Microbiological investigations were all consistently negative. Severe hip disease resulted in considerable ongoing symptoms and disability. Six cases were treated with disease-modifying anti-rheumatic drugs. Total hip replacement has been required in four patients to date, with major functional improvement. Conclusions. These cases represent severe and disabling primary hip disease with considerable clinical and investigational inflammatory features. Such a mode of presentation has not been described previously in the context of childhood chronic inflammatory arthritides, and may represent a separate oligoarthritis subtype of JIA

2. AZAR D, MARTIN F: Paediatric uveitis: a Sydney clinic experience. Clin Experiment Ophthalmol 32:5 468-471, 2004
   Organism: The Children's Hospital at Westmead, Sydney, New South Wales, Australia domitazar@studentusydeduauFAU - Azar, Domit
   Abstract: PURPOSE: The aim of this study was to retrospectively review uveitis cases at The Children's Hospital at Westmead, Sydney, since its inception in 1997 to 2001, including patients presenting at the Camperdown, Sydney, campus between 1989 and 1997 attending Westmead for further care. Comparison is made with international centres. METHODS: Information was obtained from medical records. RESULTS: Forty patients (53 eyes) presented, of whom 23 (57.5%) were female and 17 (42.5%) were male (mean age 6.7 years). Of 53 eyes, 35 (66%) had anterior uveitis, three (5.7%) intermediate uveitis, seven (13.2%) posterior uveitis and eight (15.1%) panuveitis. Twenty-seven (67.5%) patients had disease unilaterally and 13 (32.5%) bilaterally. Twenty-four (60%) cases were idiopathic. Seven (17.5%) cases were associated with juvenile rheumatoid arthritis, three (7.5%) with herpes zoster, two (5%) with herpes simplex, two (5%) with toxocara, one (2.5%) with toxoplasma, and one (2.5%) with ulcerative colitis. Complications included cataract in 14 (26.4%) eyes; band keratopathy in four (7.5%) eyes; macular scarring in three (5.7%) eyes; and glaucoma in four (7.5%) eyes. Last measured acuity was 6/6 for 19 (35.8%) eyes, < or =6/18 for 15 (28.3%) eyes and <6/60 for eight (15.1%) eyes. CONCLUSIONS: Despite small numbers, the comparisons of this study with some international studies, and its contrasts with other studies, are due to similarities and differences amongst these studies with respect to factors of referral bias, and the aetiological basis of disease

3. BECHTOLD S, RIPPERGER P, DALLA PR, SCHMIDT H, HAFNER R, SCHWARZ HP: Musculoskeletal and functional muscle-bone analysis in children with rheumatic disease using peripheral quantitative computed tomography. Osteoporos Int .: 2004
   Organism: Division of Pediatric Endocrinology, University Children's Hospital, Lindwurmstrasse 4, D-80337, Munich, Germany
   Abstract: Bone demineralization is a severe complication of juvenile idiopathic arthritis (JIA) and other rheumatic diseases. To identify patients, who are at risk of bone disease, musculoskeletal analysis is performed. Furthermore, a more functional approach is needed to assess, whether bone strength is adequate for muscle force and whether muscle force is adequate for body size. In patients with a chronic disease it is most important to differentiate between primary bone problems and those that are secondary to low muscle force. To implement this approach, we measured musculoskeletal parameters of the radius in 94 patients with juvenile idiopathic arthritis of different subtypes and connective tissue disease using peripheral quantitative computed tomography. The four groups consisted of patients with oligoarticular ( n=31), polyarticular ( n=27), systemic JIA ( n=20) and connective tissue disease (CTD) ( n=16). All patients with systemic JIA and CTD and 56% of the patients with polyarticular JIA were under treatment with glucocorticoids. In general, the longer the duration of the disease and the more severe the subtype of the rheumatic disease, the shorter the height and the lower the bone density and bone strength parameters. Mean height, bone mineral content (BMC) and muscle cross-sectional area (CSA) were low for age, but muscle CSA was normal for height with the exception of patients with polyarticular disease. In the systemic JIA group the ratio of BMC per muscle CSA was decreased by -1.7+/-2.7 SD ( P<0.05), suggesting that bone strength was not adequately adapted to muscle force. This was even more expressed in females than in males (14 versus 3). These patients need closer follow up and potential specific therapeutic intervention

4. BEGIC Z, TERZIC R, DINAREVIC S, BULJINA A, MEHOLJIC A: [Prognostic significance of juvenile chronic arthritis onset types]. Med Arh 58:3 163-166, 2004
   Organism: Pedijatrijska Klinika, KCU SarajevoFAU - Begic, Zijo
   Abstract: Juvenile chronic arthritis (JCA) is a disease or a group of diseases with chronic nonsuportive connective tissue inflammation. Depending of the onset of the disease and its course in the first six months there are three major types: systemic, poliyarticular and pauciarticular disease. Indicators of bad prognosis were: systemic form with signs of inflammation in the first six months, poliarticular onset and course, RF positivity, positive ANA and eye involvement. In the period from 1996 to 2002 at the Cardiology-Rheumatology Department in Sarajevo Pediatric Clinic 63 patients were addmited. Out of this 49 (78%) were new cases JCA was more frequent among school age girls 35 (57%). Systemic--onset JCA 9 patients (14%), polyarticular onset 19 patients (30%), pauciarticular onset 35 (55%). 15 (23.8%) was RF (rheumatoid factor) negative, 4 (6.3%) RF positive. Pauciarticular forms type 1 were 20 (31.7%), type II were 15 (23.8%). In 11 (17.5%) patients laboratory tests and clinical signs indicated poor prognosis. All patients with indicators of poor prognosis needed more aggressive therapy. Although JCA is the most frequent rheumatic disease and the leading cause of invalidity, and one of the most frequent chronic disease in children, we still do not know enough. The optimal treatment is still a challenge especially onset of JCA with poor prognosis

5. BRUNNER HI, KLEIN-GITELMAN MS, MILLER MJ, TROMBLEY M, BALDWIN N, KRESS A, JOHNSON AL, BARRON AC, GRIFFIN TA, PASSO MH, LOVELL DJ: Health of children with chronic arthritis: relationship of different measures and the quality of parent proxy reporting. Arthritis Rheum 51:5 763-773, 2004
   Organism: Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, OH 45229-3039, USA herminebrunner@cchmcorgFAU - Brunner, Hermine I
   Abstract: OBJECTIVE: To examine the strength of the association between different measures of health-related quality of life (HRQOL), disability, pain, and well-being in children with chronic arthritis. To evaluate whether HRQOL scores vary as a function of disability status beyond chance. To assess the quality of the parent proxy report for HRQOL as compared with disability, pain, and well-being. METHODS: Measures of HRQOL (visual analog scale [VAS] of health, Pediatric Quality of Life Inventory [PedsQL], Juvenile Arthritis Quality of Life Questionnaire (JAQQ), and modified standard gamble technique [SG]), disability (Childhood Health Assessment Questionnaire), VAS of pain, and VAS of well-being (VAS-well) were completed by the parents (n = 119) and patients > or =8 years (SG: > or =12 years). RESULTS: HRQOL was highest when measured by the SG, whose utilities were no more than weakly correlated with any of the other outcomes. The values of all other HRQOL measures were at least moderately correlated with each other and with the VAS-well. Irrespective of the measure used, disability was associated with significantly decreased HRQOL. There was fair to good agreement and moderate consistency of the HRQOL ratings (SG: fair consistency) between patients and parents with marked differences between health domains. CONCLUSION: HRQOL measured by the PedsQL, JAQQ, and VAS are moderately to highly correlated with each other in children with chronic arthritis. The children's HRQOL significantly decreases with increasing disability. Despite more pronounced differences for some health domains, parents are moderate to good proxy reporters of HRQOL, disability, and well-being of children with chronic arthritis

6. CASSONE R, FALCONE A, ROSSI F, MAGNI-MANZONI S, FELICI E, BUONCOMPAGNI A, MARTINI A, RAVELLI A: Unilateral destructive wrist synovitis in juvenile idiopathic arthritis. Clin Exp Rheumatol 22:5 637-642, 2004
   Organism: Dipartimento di Pediatria, Universita di Genova, Pediatria II, Istituto di Ricovero e Cura a Carattere Scientifico G Gaslini, Genova, ItalyFAU - Cassone, R
   Abstract: OBJECTIVE: To describe the clinical and radiographic features of a group of juvenile idiopathic arthritis (JIA) patients who developed unilateral destructive wrist synovitis. METHODS: All wrist radiographs performed yearly between 1986 and 2002 in JIA patients who had wrist involvement were retrospectively reviewed to identify patients who had unilateral erosive wrist synovitis, defined as a difference of at least -3 units in the Poznanski score between the affected wrist and the unaffected wrist, with the Poznanski score in the unaffected wrist being > -2 units throughout the follow-up period. Clinical and radiographic data obtained during follow-up were recorded for all patients. RESULTS: Of a total of 250 patients for whom we had approximately 900 wrist radiographs, 6 patients were found to have unilateral erosive wrist synovitis. The JIA onset subtype was oligoarticular in 5 patients and polyarticular in 1 patient and the disease duration from presentation to the last follow-up visit ranged from 2 to 16 years. The arthritis course was polyarticular in all patients. Five patients had positive antinuclear antibodies (ANA) and 1 had positive rheumatoid factor (RF). At the last follow-up visit, all patients had some impairment of wrist function and 2 patients had wrist subluxation. There was a marked radiographic damage in all affected wrist, with the Poznanski ranging from -8.0 to -8.50 units in 3 patients and being -5.5, -3.1 and -2.4 units, respectively, in 3 patients. The severity of radiographic damage in the ANA-positive patients with the longest disease duration was comparable to that observed in the RF-positive patient. CONCLUSION: Unilateral erosive wrist synovitis seems to be uncommon in JIA. Patients with unilateral wrist synovitis may be at risk of a destructive course irrespective of the JIA onset subtype

7. CHIESA S, PRIGIONE I, MORANDI F, BUONCOMPAGNI A, PICCO P, BOCCA P, MARTINI A, PISTOIA V, GATTORNO M: Cytokine flexibility of early and differentiated memory T helper cells in juvenile idiopathic arthritis. J Rheumatol 31:10 2048-2054, 2004
   Organism: 2nd Division of Pediatrics, "G Gaslini" Scientific Institute for Children, Genoa, ItalyFAU - Chiesa, Sabrina
   Abstract: OBJECTIVE: It has been suggested that CD45RO+CD27+ T cells represent recently activated memory cells, whereas CD45RO+CD27- T cells are activated memory T cells in the process of differentiating into effector cells. We investigated (1) CCR7 and CCR5 expression and (2) modulation of cytokine expression in "early" (CD27+) and "differentiated" (CD27-) memory CD4+ T cells from peripheral blood and synovial fluid (SF) of patients with juvenile idiopathic arthritis (JIA). METHODS: SF CD4+CD45RO+CD27+ and CD27- memory T cells from 6 patients with JIA were tested by flow cytometry for intracellular interferon-gamma (IFN-gamma) and interleukin 4 (IL-4) after in vitro priming with CD3 and CD28 mAb in the presence of IL-4, and subsequent culture with IL-2. RESULTS: SF CD4+CD45RO+CD27+ cells contained higher proportions of CCR7+ (median 46% vs 23%) and lower proportions of CCR5+ (73% vs 90%) cells than paired CD27- T cells. Both CD27+ and CD27- memory T helper cells from SF displayed a higher IFN-gamma/IL-4 ratio than their peripheral blood counterparts. No significant difference was observed in the percentage of IFN-gamma-expressing cells between CD27+ (32%, range 4-47%) and CD27- (29.4%, range 5-52%) memory T helper cells from SF. CONCLUSION: Irrespective of their differentiation stage, both CD27+ and CD27- SF memory T helper cells were found to switch from a proinflammatory to an antiinflammatory pattern of cytokine production

8. CLEARY AG, LANCASTER GA, ANNAN F, SILLS JA, DAVIDSON JE: Nutritional impairment in juvenile idiopathic arthritis. Rheumatology (Oxford) 43:12 1569-1573, 2004
   Organism: Department of Rheumatology, Royal Liverpool Children's Hospital, Eaton Road, Liverpool L12 2AP, UK gavincleary@rlch-trnwestnhsukFAU - Cleary, A G
   Abstract: OBJECTIVE: To investigate the relationship between nutritional impairment, measured by body mass index (BMI), expressed as an age- and sex-standardized standard deviation score (BMI SDS), and disease and patient characteristics in a UK cohort of children with juvenile idiopathic arthritis (JIA). A subgroup with available dietary information were analysed separately. METHODS: Important disease and patient characteristics (age, gender, disease subtype, swollen joint count, painful joint count, restricted joint count, treatment and dietary assessment) were assessed as potential explanatory measures of BMI SDS in a multiple linear regression. RESULTS: Data were collected on 123 consecutive patients. Twenty were nutritionally impaired. In multiple regression analysis excluding the dietary data, disease subtype [persistent oligoarthritis and polyarthritis (rheumatoid factor-negative)], five or more joints with reduced range of movement and being younger were associated with lower BMI SDS (P<0.001). When energy and protein intake were included in the analysis for a subgroup of children, the resulting model retained only disease subtype as a predictor of a low BMI SDS (P = 0.013). CONCLUSIONS: In this unselected population of children with JIA, 16% had evidence of undernutrition. The most commonly affected subtype was oligoarthritis, a previously unreported finding. There is no evidence from this study that this nutritional impairment results from inadequate food intake and it is likely that it is multifactorial in aetiology, disease subtype being the most important factor

9. DOLEZALOVA P, NEMCOVA D, CHLADEK J, KRIJT J, HOZA J: Methotrexate in rheumatic diseases in children
   METOTREXAT U DETSKYCH REVMATICKYCH ONEMOCNENI. Ceska Revmatologie (Czech Republic ) 12:3 111-119, 2004
   Abstract: Methotrexate (MTX) is one of the most effective and commonly used drugs in paediatric rheumatology. Both the total dose of MTX and its biological availability as well as the type and activity of metabolic processes involved determine the ultimate therapeutic efficacy. For the most rational and effective therapy knowledge of the principles of MTX pharmacokinetics is highly relevant mainly in terms of determination of individual dosing and route of administration. Children often need higher dose of MTX per surface area unit (10-15 mg/mSUP2/week) than adults to achieve the clinical effect. In about 30-50 % of paediatric patients parenteral, usually subcutaneous administration is necessary. Due to the short biological half-life of free MTX it appears likely that long-lived MTX metabolites (polyglutamates), that reach their stable intracellular concentration within about 6 weeks of administration, are responsible for its long-term effects. The authors summarise results of erythrocyte MTX polyglutamate concentration measurments in patients treated with MTX for Juvenile Idiopathic Arthritis. Although it is likely that it reflects biological availability of MTX usefulness of MTX polyglutamate assessment in routine therapeutic monitoring needs to be further studied. Precise mechanism of MTX action is not fully understood. Results of experimental as well as clinical studies suggest its anti-inflammatory effect is mediated by different than anti-proliferative mechanisms that are responsible mainly for its side effects. The authors present existing evidence for adenosine as the mediator of MTX anti-inflammatory action and show results of their own study dealing with blood adenosine assessment in the patients treated with MTX and matched paediatric controls. Effective MTX dose did not affect long-term adenosine concentration in treated patients. Possible explanations to this finding are discussed

10. DOZMOROV I, KNOWLTON N, TANG Y, SHIELDS A, PATHIPVANICH P, JARVIS JN, CENTOLA M: Hypervariable genes--experimental error or hidden dynamics. Nucleic Acids Res 32:19 e147, 2004
    Organism: Department of Arthritis and Immunology, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA igor-dozmorov@omrfouhsceduFAU - Dozmorov, Igor
    Abstract: In a homogeneous group of samples, not all genes of high variability stem from experimental errors in microarray experiments. These expression variations can be attributed to many factors including natural biological oscillations or metabolic processes. The behavior of these genes can tease out important clues about naturally occurring dynamic processes in the organism or experimental system under study. We developed a statistical procedure for the selection of genes with high variability denoted hypervariable (HV) genes. After the exclusion of low expressed genes and a stabilizing log-transformation, the majority of genes have comparable residual variability. Based on an F-test, HV genes are selected as having a statistically significant difference from the majority of variability stabilized genes measured by the 'reference group'. A novel F-test clustering technique, further noted as 'F-means clustering', groups HV genes with similar variability patterns, presumably from their participation in a common dynamic biological process. F-means clustering establishes, for the first time, groups of co-expressed HV genes and is illustrated with microarray data from patients with juvenile rheumatoid arthritis and healthy controls

11. HEDNER T, SAMULESSON O, WAHRBORG P, WADENVIK H, UNG KA, EKBOM A: Nabumetone: therapeutic use and safety profile in the management of osteoarthritis and rheumatoid arthritis. Drugs 64:20 2315-2343, 2004
    Organism: Department of Clinical Pharmacology, Sahlgrenska University Hospital, Goteborg, Sweden thomashedner@pharmguseFAU - Hedner, Thomas
    Abstract: Nabumetone is a nonsteroidal anti-inflammatory prodrug, which exerts its pharmacological effects via the metabolite 6-methoxy-2-naphthylacetic acid (6-MNA). Nabumetone itself is non-acidic and, following absorption, it undergoes extensive first-pass metabolism to form the main circulating active metabolite (6-MNA) which is a much more potent inhibitor of preferentially cyclo-oxygenase (COX)-2. The three major metabolic pathways of nabumetone are O-demethylation, reduction of the ketone to an alcohol, and an oxidative cleavage of the side-chain occurs to yield acetic acid derivatives. Essentially no unchanged nabumetone and < 1% of the major 6-MNA metabolite are excreted unchanged in the urine from which 80% of the dose can be recovered and another 10% in faeces. Nabumetone is clinically used mainly for the management of patients with osteoarthritis (OA) or rheumatoid arthritis (RA) to reduce pain and inflammation. The clinical efficacy of nabumetone has also been evaluated in patients with ankylosing spondylitis, soft tissue injuries and juvenile RA. The optimum oral dosage of nabumetone for OA patients is 1 g once daily, which is well tolerated. The therapeutic response is superior to placebo and similar to nonselective COX inhibitors. In RA patients, nabumetone 1 g at bedtime is optimal, but an additional 0.5-1 g can be administered in the morning for patients with persistent symptoms. In RA, nabumetone has shown a comparable clinical efficacy to aspirin (acetylsalicylic acid), diclofenac, piroxicam, ibuprofen and naproxen. Clinical trials and a decade of worldwide safety data and long-term postmarketing surveillance studies show that nabumetone is generally well tolerated. The most frequent adverse effects are those commonly seen with COX inhibitors, which include diarrhoea, dyspepsia, headache, abdominal pain and nausea. In common with other COX inhibitors, nabumetone may increase the risk of GI perforations, ulcerations and bleedings (PUBs). However, several studies show a low incidence of PUBs, and on a par with the numbers reported from studies with COX-2 selective inhibitors and considerably lower than for nonselective COX inhibitors. This has been attributed mainly to the non-acidic chemical properties of nabumetone but also to its COX-1/COX-2 inhibitor profile. Through its metabolite 6-MNA, nabumetone has a dose-related effect on platelet aggregation, but no effect on bleeding time in clinical studies. Furthermore, several short-term studies have shown little to no effect on renal function. Compared with COX-2 selective inhibitors, nabumetone exhibits similar anti-inflammatory and analgesic properties in patients with arthritis and there is no evidence of excess GI or other forms of complications to date

12. KYNGAS H: Support network of adolescents with chronic disease: adolescents' perspective. Nurs Health Sci 6:4 287-293, 2004
    Organism: University of Oulu, Department of Nursing and Health Administration, University Hospital, Oulu, Finland helvikyngas@oulufiFAU - Kyngas, Helvi
    Abstract: The purpose of this study was to describe the support network of adolescents with a chronic disease from their own perspective. Data were collected by interviewing adolescents with asthma, epilepsy, juvenile rheumatoid arthritis (JRA) and insulin-dependent diabetes mellitus (IDDM). The sample consisted of 40 adolescents aged between 13 and 17 years. Interview data were examined using content analysis. Six main categories were established to describe the support network of adolescents with a chronic disease: parents, peers, school, health care providers, technology and pets. Peers were divided into two groups: fellow sufferers and peers without a chronic disease. At school, teachers, school nurses and classmates were part of the support network. Health care providers included nurses, physicians and physiotherapists. Technology was also part of the support network and included four techniques that may be used to communicate: computers, mobile telephones, television and videos. The results provided a useful insight into the social network of adolescents with chronic disease and serve to raise awareness of the problems and opinions experienced by adolescents with this condition

13. LAMB RM, ZEGGINI E, ET AL MA, THOMSON W, DONN R: Toll-like receptor 4 (TLR4) gene polymorphisms and susceptibility to juvenile idiopathic arthritis. Ann Rheum Dis .: 2004
    Organism: Arthritis Research Campaign's Epidemiology Unit, United Kingdom
    Abstract: OBJECTIVES: To determine if polymorphisms within the Toll-like receptor 4 (TLR4) gene are associated and linked with juvenile idiopathic arthritis (JIA). To investigate any possible gene-gene (epistatic) interaction between TLR4 and macrophage migration inhibitory factor (MIF) gene polymorphisms. METHODS: Three hundred and thirteen simplex families (each containing one affected JIA proband) were available for genotyping. Two known functionally important single nucleotide polymorphisms (SNPs) within the TLR4 gene (Asp299Gly and Thr399Ile) were typed by SNaPshot(TM) ddNTP primer extension and capillary electrophoresis. Single-point and multipoint transmission disequilibrium tests (TDT) were carried out through the ETDT and TDTPHASE packages for the two TLR4 SNPs. Epistatic interaction between TLR4 haplotypes and the previously JIA associated MIF CATT7-MIF-173*C promoter haplotype was investigated using the chi(2) test and unconditional logistic regression in Stata v.7. RESULTS: No distortion from random inheritance was observed by single point analysis for TLR4 Asp299Gly (p=0.89) or TLR4 Thr399Ile (p=0.40). Similarly, no distortion in transmission was seen when the TLR4 haplotypes were studied (p=0.54). In addition, no evidence for gene-gene interaction between the TLR4 polymorphisms and the previously associated MIF gene polymorphisms were found in this cohort (p=0.40). CONCLUSIONS: No linkage or association was observed for either the Asp299Gly or the Thr399Ile SNPs of TLR4 with JIA susceptibility. Also, no evidence of an epistatic interaction between these TLR4 polymorphisms and MIF polymorphisms was found

14. MERINO R, DE INOCENCIO J, GARCIA-MIGUEL P, GARCIA-CONSUEGRA J: Lymphoproliferative disorders in paediatric rheumatic diseases. A report of two cases. Clin Exp Rheumatol 22:5 649-650, 2004
    Organism: Paediatric Rheumatology Unit, University Hospital La Paz, Madrid, Spain reumapedhulp@saludmadridorgFAU - Merino, R
    Abstract: Lymphoproliferative disorders (LPD) are reported with a much lower frequency in children with rheumatic diseases than in their adult counterparts. We describe 2 patients who developed a lymphoma during the course of the disease. The first is a 16-year-old girl diagnosed with systemic juvenile idiopathic arthritis 6 years before who developed a mucosa-associated lymphoid tissue (MALT) lymphoma. The second report involves a boy diagnosed with systemic lupus erythematosus at 9 years of age who developed a Hodgkin's lymphoma 9 years after the disease onset. In spite of the low frequency of LPD in children with rheumatic diseases, these processes do occur

15. NIANG A, DIALLO S, KA MM, POUYE A, DIOP S, NDONGO S, DIOP TM: [Hemophagocytic syndrome complicating adult's seropositive rheumatoid arthritis]. Rev Med Interne 25:11 826-828, 2004
    Organism: Clinique medicale 1, CHU A-Le-Dantec, Dakar, Senegal niangabdou@yahoocom <niangabdou@yahoocom>FAU - Niang, A
    Abstract: INTRODUCTION: Macrophage activation syndrome (MAS) is a severe complication of chronic rheumatic diseases, particularly juvenile rheumatoid arthritis. However, MAS is rarely described in adult rheumatoid polyarthritis. EXEGESE: We report a case of MAS complicating a seropositive rheumatoid polyarthritis after 20 years of evolution. Pancytopenia with fever, renal failure and hepatic dysfunction revealed the disease that was confirmed by multiple macrophages and monocytes invading the bone marrow specimen. CONCLUSION: Outcome has been spectacular under corticosteroids

16. PAPP KA: Etanercept in psoriasis. Expert Opin Pharmacother 5:10 2139-2146, 2004
    Organism: Probity Medical Research, 135 Union Street East, Waterloo, ON N2J 1C4, Canada kapapp@probitymedicalcomFAU - Papp, Kim A
    Abstract: Psoriasis is a chronic skin disorder that affects approximately 2% of the US and European populations. Several lines of evidence have demonstrated the correlation between elevated levels of TNF and psoriasis, suggesting that interfering with the inflammatory effects of TNF may help resolve psoriatic lesions. The biological agent, etanercept, is a fully human soluble TNF-receptor fusion protein with proven efficacy in the treatment of rheumatoid arthritis, ankylosing spondylitis, juvenile rheumatoid arthritis, and psoriatic arthritis. In several well-controlled clinical trials, etanercept showed sustained efficacy in reducing the signs and symptoms of psoriasis in patients with moderate-to-severe disease. With the exception of injection site reactions, adverse event rates were similar to placebo and did not increase across higher doses. No opportunistic infections, including tuberculosis, were reported. From analysis of the available clinical trials, etanercept appears to be an effective and well-tolerated agent for the treatment of moderate-to-severe psoriasis

17. PRENDIVILLE JS, TUCKER LB, CABRAL DA, CRAWFORD RI: A pruritic linear urticarial rash, fever, and systemic inflammatory disease in five adolescents: adult-onset still disease or systemic juvenile idiopathic arthritis sine arthritis? Pediatr Dermatol 21:5 580-588, 2004
    Organism: Division of Pediatric Dermatology, Department of Pediatrics, British Columbia's Children's Hospital, Vancouver, British Columbia, CanadaFAU - Prendiville, Julie S
    Abstract: The characteristic rash of systemic juvenile idiopathic arthritis is a transient erythematous eruption associated with a quotidian spiking fever. Usually asymptomatic, it can be pruritic, with dermatographism at sites of scratching or pressure. An illness similar to this entity in adults is designated adult-onset Still disease. The relationship between the pediatric and adult disease is uncertain and differences in case definition have evolved. Specifically, a sustained arthritis for at least 6 weeks is required for a diagnosis of systemic juvenile idiopathic arthritis, whereas transient arthritis and arthralgia are accepted criteria in adult-onset Still disease. We describe five patients less than 16 years of age who presented with an acute illness characterized by fever and a distinctive skin eruption. Intense pruritus and linear erythematous lesions flared with a spiking fever, usually in the late afternoon and evening. Periorbital edema/erythema and nonlinear urticarial lesions were also seen. Two children had splinter hemorrhages of the nail beds and one girl developed a fixed, scaling, pigmented, linear eruption. Severe malaise, myalgia, arthralgia, and leukocytosis were present in every patient. Other systemic manifestations included sore throat, transient arthritis, abdominal pain, lymphadenopathy, hepatomegaly, splenomegaly, hyperferritinemia, and hepatic dysfunction. No patient had a sustained arthritis. The course of the disease was variable. One patient, diagnosed with macrophage activation syndrome, recovered on oral naproxen. Two patients responded to systemic corticosteroid therapy. One girl developed status epilepticus and died from aspiration and asphyxia. A boy with severe hepatitis developed renal failure and thrombotic thrombocytopenic purpura and was treated with plasmapheresis, dialysis, and systemic corticosteroids; he had recurrent episodes of rash and fever into adult life. These children did not fulfill the case definition of systemic juvenile idiopathic arthritis because they lacked a persistent arthritis. Adolescent and adult patients with the same clinical and laboratory findings are described under the rubric of adult-onset Still disease. Recognition of the distinctive urticarial skin eruption and spiking fever is important in the diagnosis of a disease with severe morbidity and potentially life-threatening complications

18. RAMANAN AV, ROSENBLUM ND, FELDMAN BM, LAXER RM, SCHNEIDER R: Favorable outcome in patients with renal involvement complicating macrophage activation syndrome in systemic onset juvenile rheumatoid arthritis. J Rheumatol 31:10 2068-2070, 2004
    Organism: Department of Pediatrics, Health Policy Management and Evaluation, and Public Health Sciences, Hospital for Sick Children, University of Toronto, Toronto, Ontario, CanadaFAU - Ramanan, Athimalaipet V
    Abstract: Systemic-onset juvenile rheumatoid arthritis (SoJRA) constitutes about 10-20% of all JRA. However more than two-thirds of the mortality seen in JRA patients is accounted for by SoJRA. Macrophage activation syndrome (MAS), which can also be considered as a form of secondary hemophagocytic lymphohistiocytosis, is a major cause of morbidity and mortality in children with SoJRA. MAS is characterized by persistent high fever, pancytopenia, mild to serious derangements of liver cell function, encephalopathy, and disseminated intravascular coagulation. Renal involvement in MAS is a rarely recognized feature. In 2 recently reported case series of MAS in SoJRA, renal involvement appeared to be associated with poor prognosis. We describe 3 children with SoJRA who had renal involvement complicating MAS and had a favorable outcome

19. RUTKOWSKA-SAK L, RYZKO J, WAGNER TERESA, LEGATOWICZ-KOPROWSKA M: Gastrointestinal system involvement in juvenile idiopathic arthritis complicated with amyloidosis. Reumatologia (Warsaw) 42:1 5-19, 2004
    Abstract: Functional and morphological changes of the gastrointestinal system were assessed in patients suffering from juvenile idiopathic arthritis complicated with amyloidosis. The results of endoscopic investigation of the gastrointestinal tract showed amyloidosis and inflammatory changes, cardiac and pylorus atony and refluxes. Ultrasonography results suggested hepatic, bile ducts and pancreatic inflammatory changes, steatosis and/or amyloidosis, dyskinesis. The above - mentioned changes were confirmed by morphological investigation (biopsy and/or autopsy). The results of the capacity tests performed in patients revealed an impairment hypoacidity and reduced gastric juice secretion, high serum gastrin level, distrubance liver detoxication function and pancreas and bowel functional capacity as well. Additionally, intolerance against lactose, casein and alfa- and beta-lactoglobuline was found in most of the patients. Some symptoms of malnutrition and malabsorption were observed in all of them. Such factors as underlying disease severity, adverse drug effects, environmental factors (infections, nutrition) were taken into consideration as probable causes of the gastrointestinal system damage

20. TYNJALA P, HONKANEN V, LAHDENNE P: Intra-articular steroids in radiologically confirmed tarsal and hip synovitis in juvenile idiopathic arthritis. Clinical and Experimental Rheumatology (Italy ) 22:5 643-648, 2004
    Abstract: Objective. To estimate the value of MRI or US imaging in the diagnosis of synovitis and the response to local steroid therapy in tarsal and hip synovitis. Methods. 32 patients with juvenile idiopathic arthritis (JIA), 19 of them with 22 tarsal and 13 of them with 20 hip synovitis, were followed up for 12 months after intra-articular corticosteroid treatment (IAST). MRI was taken from swollen ankles/feet to target the inflamed area before IAST. The synovitis in hip joints was assessed by both clinical and ultrasonographic examination. Results. MRI showed that in the swollen tarsal area the inflammation was distributed widely in the joints and tendon sheaths. In 13/22 (59%) ankles/feet, synovitis was observed in multiple joint spaces. In 17/22 (77%) ankles/feet, tenosynovitis was present. In 32% of cases, the IAST induced clinical remission for up to 12 months. In hip synovitis, ultrasound supplemented clinical assessment. At 12 months after IAST, a successful treatment response was seen in 10/20 (50%) hips. Conclusion. In unresponsive tarsal arthritis, the synovitic sites should be targeted by radiological imaging to improve the efficacy of corticosteroid infections. For pediatric rheumatologists, easy access to US is preferable to optimize the treatment of hip and tarsal synovitis in JIA. (c) Copyright Clinical and Experimental Rheumatology 2004

21. VERBSKY JW, WHITE AJ: Effective use of the recombinant interleukin 1 receptor antagonist anakinra in therapy resistant systemic onset juvenile rheumatoid arthritis. J Rheumatol 31:10 2071-2075, 2004
    Organism: Division of Rheumatology, Department of Pediatrics, Washington University School of Medicine, St Lousis Children's Hospital, Missouri 63110, USAFAU - Verbsky, James W
    Abstract: Systemic onset juvenile rheumatoid arthritis (SOJRA) is a multisystem disease characterized by high fever, rash, arthritis, serositis, splenomegaly, and laboratory evidence of systemic inflammation. Anticytokine therapies show promise in the treatment of chronic arthritides in children. We describe the use of the recombinant interleukin 1 receptor antagonist anakinra in 2 patients with therapy resistant SOJRA. Both patients experienced immediate and sustained resolution of symptoms and laboratory markers of inflammation, in one case after years of treatment with other immunosuppressive therapies

22. ZHOU H, PARKS V, PATAT A, LE COZ F, SIMCOE D, KORTH-BRADLEY J: Absence of a clinically relevant interaction between etanercept and digoxin. J Clin Pharmacol 44:11 1244-1251, 2004
    Organism: Clinical Pharmacology, Wyeth Research, 500 Arcola Road, Collegeville, PA 19426, USAFAU - Zhou, Honghui
    Abstract: Etanercept, a soluble recombinant human tumor necrosis factor receptor (TNFr), is effective and well tolerated in the treatment of rheumatoid arthritis, juvenile rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, and psoriasis. The primary objective of this study was to investigate the potential pharmacokinetic and pharmacodynamic interaction between digoxin and etanercept at steady state. In a crossover, open-label, nonrandomized, 3-period study, 12 healthy male subjects received loading oral doses of digoxin 0.5 mg every 12 hours on day 1 and 0.25 mg every 12 hours on day 2, followed by a daily maintenance dose of 0.25 mg for a total of 27 days. Etanercept was administered as a twice-weekly 25-mg subcutaneous dose beginning on day 9 and continuing up to day 37 for a total of 9 doses. All ratios of maximum plasma concentration (C(max)) and area under the plasma concentration versus time curve (AUC) for pharmacokinetics of digoxin fell within the confidence interval of 0.8 to 1.25. Although not considered clinically relevant, the mean C(max) and AUC of etanercept were 4.2% and 12.5% lower, respectively, when etanercept was given with digoxin than when administered alone. There were no clinically relevant changes in the electrocardiogram (ECG) parameters, and adverse events did not increase when both drugs were combined. In conclusion, there is no clinically relevant interaction between etanercept and digoxin, and both drugs can be safely coadministered without the need for a dosage adjustment