Bibliography September 04

1. [Immunologic peculiarities of uveitis concurrent with systemic pathologies]. Vestn Oftalmol 120:4 24-26, 2004
   Abstract: Immunologic examinations were performed in 111 patients with uveitis concurrent with a variety of systemic pathologies, including 85 males and 26 females, mean age--32.4 +/- 5.8. A higher IL-6 content in blood serum (BS) and in lachrymal fluid (LF) was detected in all patients. The IL-4 content was lower in uveitis associated with ankylosing spondylitis and with Reuter's disease, whereas, it was higher in juvenile rheumatoid arthritis. The systemic immunity changes were related with the hemostasis impairments in the phagocytic, humoral and cellular chains: an enhanced functional activity of phagocyte cells, a lower absolute quantity of T-lymphocytes, a higher count of B-cells, a reduced concentration of IgM and of circulating immune complexes (CIC), and a diminished general hemolytic activity of the complement in BS. A reduced concentration of the secretory fraction of IgA, IgG and IgM concurrent with higher concentrations of IgA, C3- and C4 complement components, CIC and of lysozyme activity in LF was detected in the local immunity system

2. BARNES MG, ARONOW BJ, LUYRINK LK, MOROLDO MB, PAVLIDIS P, PASSO MH, GROM AA, HIRSCH R, GIANNINI EH, COLBERT RA, GLASS DN, THOMPSON SD: Gene expression in juvenile arthritis and spondyloarthropathy: Pro-angiogenic ELRSUP+ chemokine genes relate to course of arthritis. Rheumatology (United Kingdom ) 43:8 973-979, 2004
   Abstract: Objective. To evaluate the ability of microarray-based methods to identify genes with disease-specific expression patterns in peripheral blood mononuclear cells (PBMC) and synovial fluid mononuclear cells (SFMC) of juvenile arthritis patients and healthy controls. Methods. Microarray data (Affymetrix U95Av2) from 26 PBMC and 20 SFMC samples collected from patients with active disease (classified by course according to ACR criteria) were analysed for expression patterns that correlated with disease characteristics. For comparison, PBMC gene expression profiles were obtained from 15 healthy controls. Real-time PCR was used for confirmation of gene expression differences. Results. Statistical analysis of gene expression patterns in PBMC identified 378 probe sets corresponding to 342 unique genes with differing expression levels between polyarticular course patients and controls (t test P < 0.0001). The genes represented by these probe sets were enriched for functions related to regulation of immune cell functions, receptor signalling as well as protein metabolism and degradation. Included in these probe sets were a group of CXCL chemokines with functions related to angiogenesis. Further analysis showed that, whereas angiogenic CXCL (ELRSUP+) gene expression was elevated in polyarticular PBMC, expression of angiostatic CXCL (ELRSUP-) chemokines was lower in polyarticular SFMC compared with corresponding pauciarticular samples (t test, P < 0.05). Conclusions. This pilot study demonstrates that juvenile arthritis patients exhibit complex patterns of gene expression in PBMC and SFMC. The presence of disease-correlated biologically relevant gene expression patterns suggests that the power of this approach will allow better understanding of disease mechanisms, identify distinct clinical phenotypes in disease subtypes, and suggest new therapeutic approaches. (c) British Society for Rheumatology 2004; all rights reserved

3. BENNERMO M, HELD C, STEMME S, ERICSSON CG, SILVEIRA A, GREEN F, TORNVALL P: Genetic Predisposition of the Interleukin-6 Response to Inflammation: Implications for a Variety of Major Diseases? Clin Chem .: 2004
   Organism: Department of Medicine, Danderyd University Hospital, Stockholm, Sweden
   Abstract: BACKGROUND: A single-nucleotide polymorphism (SNP) in the promoter region of the interleukin-6 (IL-6) gene at position -174 (G>C) has been reported to be associated with a variety of major diseases, such as Alzheimer disease, atherosclerosis, and cardiovascular disease, cancer, non-insulin-dependent diabetes mellitus, osteoporosis, sepsis, and systemic-onset juvenile chronic arthritis. However, authors of previous in vitro and in vivo studies have reported conflicting results regarding the functionality of this polymorphism. We therefore aimed to clarify the role of the -174 SNP for the induction of IL-6 in vivo. METHODS: We vaccinated 20 and 18 healthy individuals homozygous for the -174 C and G alleles, respectively, with 1 mL of Salmonella typhii vaccine. IL-1beta, IL-6, and tumor necrosis factor-alpha (TNF-alpha) were measured in the blood at baseline and up to 24 h after vaccination. RESULTS: Individuals with the G genotype had significantly higher plasma IL-6 values at 6, 8, and 10 h after vaccination than did individuals with the C genotype (P <0.01). There were no differences between the two genotypes regarding serum concentrations of IL-1beta and TNF-alpha before or after vaccination. CONCLUSIONS: The -174 G>C SNP in the promoter region of the IL-6 gene is functional in vivo with an increased inflammatory response associated with the G allele. Considering the central role of IL-6 in a variety of major diseases, the present finding might be of major relevance

4. BODMAN-SMITH MD, FIFE MF, WYTHE H, CORRIGAL VM, PANAYI GS, WEDDERBURN LR, WOO P: Anti-BiP antibody levels in juvenile idiopathic arthritis (JIA). Rheumatology (Oxford) 43:10 1305-1306, 2004
   Organism: mbodmans@sghmsacukFAU - Bodman-Smith, M D

5. CARVOUNIS PE, HERMAN DC, CHA SS, BURKE JP: Ocular manifestations of juvenile rheumatoid arthritis in Olmsted County, Minnesota: a population-based study. Graefes Arch Clin Exp Ophthalmol .: 2004
   Organism: Department of Ophthalmology, The George Washington University, Suite 2A, 2150 Pennsylvania Ave NW, 20037, Washington, DC, USA
   Abstract: BACKGROUND. Juvenile rheumatoid arthritis (JRA) is the most common systemic cause of uveitis in Europe and North America. The cumulative incidence of uveitis in JRA has been reported at between 8.5% and 25% in series from referral centers in the USA. There have been no population-based studies of the cumulative incidence of uveitis in JRA in the USA. METHODS. We performed a population-based, retrospective cohort study of patients residing in Olmsted County, Minnesota between 1 January 1960 and 31 December 2000 who met American College of Rheumatology diagnostic criteria for JRA. The patients were identified using the Rochester Epidemiology Project (REP), a surveillance and medical records-linkage system which provides access to medical records of residents of Olmsted County. Patient histories were reviewed and information regarding rheumatic and ocular disease was extracted and analyzed. The main outcome measures were: cumulative incidence of uveitis, of complications of uveitis, of keratoconjunctivitis sicca (KCS) and of adverse visual outcome. RESULTS. Of the 88 patients identified, three patients developed uncomplicated uveitis [3.4%; 95% confidence intervals [CI] 0.7-9.6%), all with pauciarticular onset JRA. Two patients developed KCS (2.3%; 95% CI 0.3-8.0%). The visual acuity of these five patients at last follow-up (mean length of follow-up 22.6 years, range 8-36 years) was 20/20. There were no patients with visual loss attributable to JRA. CONCLUSIONS. In a population-based study of JRA in the United States, uveitis occurred at a lower frequency than expected. In the limited number of cases in this cohort with JRA-associated ophthalmologic complications there was no resulting loss of visual acuity

6. CIL A, ATAY OA, AYDINGOZ U, TETIK O, GEDIKOGLU G, DORAL MN: Bilateral lipoma arborescens of the knee in a child: a case report. Knee Surg Sports Traumatol Arthrosc .: 2004
   Organism: Department of Orthopaedics and Traumatology, Hacettepe University Medical Center, 06100, Sihhiye-Ankara, Turkey
   Abstract: We report a case of childhood lipoma arborescens of both knee joints who had been erroneously diagnosed to have initially acute rheumatic fever and subsequently oligoarticular juvenile rheumatoid arthritis. She had taken anti-inflammatory medication for 8 years without remission of the effusion. Magnetic resonance imaging (MRI) and synovectomy revealed the diagnosis of lipoma arborescens. Lipoma arborescens should be kept in mind in the differential diagnosis of refractory chronic joint effusion and synovial hypertrophy in the childhood period, and MRI yields the correct diagnosis in this setting

7. DE KLEER IM, BRINKMAN DM, FERSTER A, ABINUN M, QUARTIER P, VAN DER NJ, TEN CATE R, WEDDERBURN LR, HORNEFF G, OPPERMANN J, ZINTL F, FOSTER HE, PRIEUR AM, FASTH A, VAN ROSSUM MA, KUIS W, WULFFRAAT NM: Autologous stem cell transplantation for refractory juvenile idiopathic arthritis: analysis of clinical effects, mortality, and transplant related morbidity. Ann Rheum Dis 63:10 1318-1326, 2004
   Organism: Paediatric BMT unit, Suite KC 03063, University Medical Centre Utrecht, PO box 85090, 3508 AB Utrecht, NetherlandsFAU - De Kleer, I M
   Abstract: OBJECTIVE: To evaluate the safety and efficacy of autologous stem cell transplantation (ASCT) for refractory juvenile idiopathic arthritis (JIA). DESIGN: Retrospective analysis of follow up data on 34 children with JIA who were treated with ASCT in nine different European transplant centres. Rheumatological evaluation employed a modified set of core criteria. Immunological reconstitution and infectious complications were monitored at three month intervals after transplantation. RESULTS: Clinical follow up ranged from 12 to 60 months. Eighteen of the 34 patients (53%) with a follow up of 12 to 60 months achieved complete drug-free remission. Seven of these patients had previously failed treatment with anti-TNF. Six of the 34 patients (18%) showed a partial response (ranging from 30% to 70% improvement) and seven (21%) were resistant to ASCT. Infectious complications were common. There were three cases of transplant related mortality (9%) and two of disease related mortality (6%). CONCLUSIONS: ASCT in severely ill patients with JIA induces a drug-free remission of the disease and a profound increase in general wellbeing in a substantial proportion of patients, but the procedure carries a significant mortality risk. The following adjustments are proposed for future protocols: (1) elimination of total body irradiation from the conditioning regimen; (2) prophylactic administration of antiviral drugs and intravenous immunoglobulins until there is a normal CD4+ T cell count

8. DOLEZALOVA P, KRIJT J, CHLADEK J, NEMCOVA D, HOZA J: Adenosine and methotrexate polyglutamate concentrations in patients with juvenile arthritis. Rheumatology (Oxford) .: 2004
   Organism: Department of Paediatrics and Adolescent Medicine, Charles University in Prague, 1st Faculty of Medicine, Czech Republic
   Abstract: Objective. In contrast to the anti-proliferative properties of high-dose methotrexate (MTX) its anti-inflammatory mechanism of action in rheumatic diseases has been attributed to increased adenosine accumulation, most likely caused by long-lived intracellular MTX polyglutamates. The aim of this study was to assess adenosine concentrations in MTX-treated and untreated children and to relate it to MTX polyglutamate concentration measured in erythrocytes and to the therapeutic efficacy. Methods. Adenosine and MTX-polyglutamate concentrations in erythrocytes (EMTX) were assessed in venous blood samples taken before the next MTX dose in 30 patients treated long-term for juvenile idiopathic arthritis (JIA) and in 16 untreated matched controls. The blood concentration of adenosine was measured by the liquid chromatography/tandem mass spectrometry (LC-MS/MS) method and EMTX by an enzymatic assay. Therapeutic efficacy was assessed using the preliminary definition of improvement in JIA patients. Results. Mean blood adenosine concentration in MTX-treated patients was 48.05 nmol/l (s.d. 10.1) vs 49.6 nmol/l (s.d. 12.5) in untreated controls (P = 0.55). Mean EMTX was 215.56 nmol/l (s.d. 212.9). No significant correlation was found between adenosine concentrations and MTX dose or EMTX (P = 0.8 and 0.6, respectively). Adenosine concentration did not differ in clinical responders when compared with non-responders (P = 0.9). Conclusions. We have shown that there is no impact of effective MTX dose represented by EMTX on blood adenosine concentration in JIA patients. If MTX anti-inflammatory action is mediated by adenosine it is likely that local release of adenosine at inflamed tissues is responsible for its action which may not be reflected by sustained increase of its blood concentration

9. FUNG L-W, GANESAN V: Arteriovenous malformations presenting with papilloedema. Developmental Medicine and Child Neurology (United Kingdom ) 46:9 626-627, 2004
   Abstract: Cerebral arteriovenous malformations (AVMs) are fairly common and the majority of paediatric patients with this condition also present with intracranial haemorrhage. Two patients who had an incidental finding of an AVM associated with papilloedema are described here. The first was a 13-year-old male who presented after an accidental kick to the eyes. Examination revealed bilateral papilloedema. He gave a 2-year history of intermittent headache. Brain magnetic resonance imaging (MRI) showed an unruptured AVM in the temporal lobe. Lumbar puncture revealed elevated cerebrospinal fluid pressure. Visual acuity and visual fields were normal. He was treated with acetazolamide and improved within a few weeks. He subsequently underwent stereotactic radiosurgery to the AVM. He discontinued acetazolamide due to adverse side effects and there was no recurrence of headache and papilloedema. The second patient was a 14-year-old male who had polyarticular juvenile chronic arthritis and received low-dose steroids and methotrexate. Bilateral papilloedema was discovered during routine ophthalmology surveillance and he was otherwise asymptomatic neurologically. Brain MRI revealed an AVM in the posterior fossa. He had three embolization procedures, which have resulted in significant reduction in lesion size. The papilloedema resolved completely after the first two procedures, and visual acuity and fields remained normal. Here, possible underlying mechanism of raised intracranial pressure and importance of visual assessment in those with AVMs and their management are discussed

10. GODINHO F, SANTOS MJ, CANAS DS: Refractory adult onset Still's disease successfully treated with anakinra. Ann Rheum Dis .: 2004
    Organism: Hospital garcia de orta - Portugal
    Abstract: Pro-inflammatory cytokines like TNF-alpha, IL-6, IL-18 and IL-1 have been implicated in the pathogenesis of several chronic rheumatic inflammatory diseases including juvenile idiopathic arthritis and adult onset Still's disease (AOSD) (1-5). The treatment of these diseases includes non-steroidal anti-inflammatory drugs (NSAIDs), systemic corticosteroids and in resistant cases, methotrexate (MTX), cyclophosphamide, sulfassalazine (SSZ) and cyclosporine A (Cp A)(6-8) have been used. Over the past years, several cases of successful treatment with infliximab and etanercept in AOSD, refractory to conventional therapy, have been published (8,9)

11. GORDON K, NORMAN N, FRANKEL E, ZITNIK R, STEVENS S, WANG H: Efficacy of etanercept in an integrated multistudy database of patients with psoriasis. Journal of Investigative Dermatology 122:3 A54, 2004

12. GOTTLIEB A, GOFFE B, VEITH J, STEVENS S, NAKANISHI A: Safety of etanercept in an integrated multistudy database of patients with psoriasis. Journal of Investigative Dermatology 122:3 A55, 2004

13. HEINZMANN A, AHLERT I, KURZ T, BERNER R, DEICHMANN KA: Association study suggests opposite effects of polymorphisms within IL8 on bronchial asthma and respiratory syncytial virus bronchiolitis. Journal of Allergy and Clinical Immunology (United States ) 114:3 671-676, 2004
    Abstract: IL-8 is a strong inductor of inflammation. Accordingly, it plays a pivotal role in acute inflammatory responses during respiratory syncytial virus (RSV) infections and in chronic inflammatory diseases such as bronchial asthma and juvenile idiopathic arthritis. Recently, 2 studies have found association of the polymorphism -251A of IL8 with RSV bronchiolitis. Furthermore, epidemiologic studies have demonstrated an increased risk for the development of asthma after RSV bronchiolitis, and a common genetic background for the 2 diseases is currently being discussed.This study investigated whether IL-8 is in association with asthma and/or arthritis and whether the results can confirm a common genetic background of RSV bronchiolitis and asthma.The polymorphisms -A251T, C781T, C1633T, and A2767T within IL8 were genotyped in the following 4 populations: children with asthma, atopic children, children with juvenile idiopathic arthritis, and control subjects. Statistical analysis made use of the Armitage trend test and the software program Arlequine.Association of all polymorphisms was found with asthma (P =. 008 to P =. 03). Surprisingly -251T was associated with asthma, which is the opposite allele as described in association with RSV bronchiolitis. Furthermore, all polymorphisms were significantly more common in children with arthritis than in asthmatic children (P =. 006 to P =. 02). No association was seen with the diagnosis of arthritis per se or with atopy.This is the first study to describe association of IL-8 with asthma and a significant inverse distribution of the polymorphisms in juvenile idiopathic arthritis. In addition, the results of this study might suggest that RSV bronchiolitis and bronchial asthma have at least some different genetic factors

14. HIRSHFELD AB, KAHLE AL, CLARK BJ, III, BRIDGES ND: Parent-reported health status after pediatric thoracic organ transplant. J Heart Lung Transplant 23:9 1111-1118, 2004
    Organism: Division of Cardiology, Department of Pediatrics, The Children's Hospital of Philadelphia and the University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USAFAU - Hirshfeld, Amy B
    Abstract: BACKGROUND: Thoracic organ transplantation is a life-changing event for a child and family from both a physical and a psychosocial perspective. Accurate pre-transplantation counseling and effective post-transplantation follow-up depend on a good understanding of post-transplantation health status, especially as perceived by families. METHODS: The Child Health Questionnaire-Parent Form 50 (CHQ-P50), an instrument that assesses parent-reported health status of pediatric patients, was administered to 47 pediatric thoracic organ transplant recipients (41 heart, 6 lung) 5 to 18 years of age. RESULTS: Transplant recipients scored lower on the Physical Health Summary (PhS) score than the general population, as evidenced by a lower median score (50.6 vs 55.1, p < 0.0001) and a difference in the distribution of quartiles (p = 0.001), skewed toward the lower quartiles of the general population. The distribution of PhS scores in transplant recipients was comparable to scores of 3 groups of pediatric patients with other chronic health conditions (juvenile rheumatoid arthritis, epilepsy and asthma). The distribution of the Psychosocial Health Summary (PsS) scores was similar to that of the general population, but the median score was lower (51.5 vs 53.2, p = 0.02). Transplant patients clearly scored lower than the general population on 4 of 12 sub-scales, including those assessing general health, physical functioning, family activities and parental emotional impact. No difference was found in sub-scales reflecting self-esteem, mental health, behavior, pain, peer interactions, family cohesion or parental time demands. CONCLUSIONS: Thoracic organ transplantation in children ages 5 to 18 years is associated with an ongoing deficit in parent-perceived physical health status

15. KUBOTA Y, NAKAYAMA J: A case of juvenile onset Sjogren's syndrome. Nishinihon Journal of Dermatology (Japan ) 66:4 336-341, 2004
    Abstract: We report a 9-year-old Japanese girl with Sjogren's syndrome. She had recurrent spiking fever and rheumatoid factor in her serum at the age of 7. One year later, she had recurrent annular erythemas on her feet without arthralgia. In a pediatric clinic, she had been treated with non-steroidal anti-inflammatory drugs under the diagnosis of juvenile rheumatoid arthritis. She had developed recurrent annular erythemas on her face and extremities beginning in October 1999, and she presented at our hospital in November 1999. Her serum was positive for anti-nuclear antibody, anti SS-A and SS-B antibodies and she had hypergammaglobulinemia. A biopsy specimen from an erythema on the left upper arm revealed liquefaction and degeneration of the basal layer, infiltration of lymphocytes and debris around the vessels and skin appendages in the dermis. At present, she manifests recurrent fever and annular erythemas. We believe that this patient has juvenile onset Sjogren's syndrome based on the recurrent fever, cervical swelling and annular erythemas, although subacute cutaneous lupus erythematosus is another differential diagnosis histopathologically

16. LACOMIS D, ROESKE-ANDERSON L, MATHIE L: Neuropathy and Fabry's disease. Muscle Nerve .: 2004
    Organism: Department of Neurology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
    Abstract: Fabry's disease is a multisystem disorder that is commonly associated with a painful, debilitating neuropathy. The common coexistence of arthralgias and an elevated erythrocyte sedimentation rate may lead to the misdiagnosis of a rheumatic condition. We report a 38-year-old man who was evaluated for progressive neuropathy and limb pain in the setting of longstanding arthralgias, presumed juvenile rheumatoid arthritis, and past renal transplantation. Histopathologic assessment of nerve and muscle biopsy specimens led to the diagnosis of Fabry's disease, thus allowing the patient to receive enzyme replacement therapy that may slow progression and preserve the transplanted kidney. Muscle Nerve 2004

17. LINDEHAMMAR H, LINDVALL B: Muscle involvement in juvenile idiopathic arthritis. Rheumatology (Oxford) .: 2004
    Organism: Department of Neuroscience and Locomotion, Division of Clinical Neurophysiology, Faculty of Health Sciences, Linkoping University, Sweden
    Abstract: Objective. An observational study of changes in muscle structure and the relation to muscle strength in juvenile idiopathic arthritis (JIA). Methods. Fifteen children and teenagers (eight girls and seven boys) with JIA, aged 9-19 yr (mean age 16.1), were studied. Muscle biopsies were obtained from the anterior tibial muscle and were examined using histopathological and immunohistochemical methods. Muscle fibre types were classified and fibre areas measured. As markers of inflammation, the major histocompatibility complex (MHC) class I and class II and the membrane attack complex (MAC) were analysed. Results were compared with biopsies from the gastrocnemius muscle in 33 young (19-23 yr) healthy controls. Isometric and isokinetic muscle strengths were measured in ankle dorsiflexion. Strength was compared with reference values for healthy age-matched controls. Nerve conduction velocities were recorded in the peroneal and sural nerves. Results. Four of the 15 muscle biopsies were morphologically normal. Eleven biopsies showed minor unspecific changes. Two of these also showed minor signs of inflammation. MHC class II expression was found in 4/15 patients, which was significantly more than in the healthy controls (P = 0.0143). The expression of MHC class I and MAC did not differ from that in the controls. The mean area of type I fibres was lower than that of type IIA fibres in 12/13 biopsies. Muscle strength was significantly reduced in the patient group. There was a significant positive correlation between muscle fibre area and muscle strength. Nerve conduction studies were normal in all cases. Conclusions. Changes in leg muscle biopsies appear to be common in children and teenagers with JIA. The presence of inflammatory cells in the muscle and expression of MHC class II on muscle fibres may be a sign of inflammatory myopathy. There are no findings of type II muscle fibre hypotrophy or neuropathy, as in adults with RA

18. LOW JM, CHAUHAN AK, KIETZ DA, DAUD U, PEPMUELLER PH, MOORE TL: Determination of anti-cyclic citrullinated peptide antibodies in the sera of patients with juvenile idiopathic arthritis. Journal of Rheumatology (Canada ) 31:9 1829-1833, 2004
    Abstract: Objective. Anti-cyclic citrullinated peptide (anti-CCP) antibodies have been found in sera of 76% of patients with rheumatoid arthritis (RA), mainly in rheumatoid factor (RF) positive patients, with a specificity of 96%. We evaluated the presence of anti-CCP antibodies in patients with juvenile idiopathic arthritis (JIA) and assessed the possibility of synthetic citrullinated peptides as antigenic determinants in JIA. Methods. The presence of anti-CCP antibodies was determined using 3 synthetic citrullinated peptide variants and 2 commercial kits (Inova Diagnostics and Axis-Shield Diagnostics) optimized for detecting JIA-specific antibodies in serum by an ELISA based assay. We evaluated 66 patients with JIA (16 RF positive polyarthritis, 18 RF negative polyarthritis, 19 oligoarthritis, and 13 systemic arthritis). We also tested 9 adult RA patients, 34 patients with systemic lupus erythematosus (SLE), and 25 healthy persons as controls. Results. Significant concentrations of anti-CCP antibodies were detected in the majority of RF positive JIA patients with polyarthritis. Using the 2 synthetic linear peptides, 12/16 (75%) were positive; 9/12 (75%) were positive with the Inova kit and 9/10 (90%) were positive with the Axis-Shield kit. However, utilizing the synthetic linear peptides, significant concentrations of anti-CCP antibodies were detected in 51/66 (77%) JIA patients, including 15/18 (83%) RF negative polyarthritis, 16/19 (84%) oligoarthritis, and 8/13 (62%) systemic arthritis patients. No healthy control showed elevated antibody levels. In contrast, 4/9 (44%) patients with adult RA and 2/6 (33%) with SLE had elevated anti-CCP levels. The synthetic cyclic variant cfc-1-cyc yielded significant anti-CCP levels for 13/14 (93%) patients with RF negative polyarthritis, 6/10 (60%) with oligoarthritis, and 3/7 (43%) with systemic arthritis, and 8/9 (88%) RF positive patients. No healthy control had increased anti-CCP levels. However, 4/9 (44%) adult RA and 9/34 (26%) SLE patients were found to have elevated anti-CCP levels. Using the Inova and Axis-Shield kits, much smaller percentages were found in the RF negative patients, with only 4/16 (25%) in the oligoarthritis and RF negative polyarthritis patients with the Inova kits and 0/25 (0%) by the Axis-Shield kits. The Inova kit revealed elevated anti-CCP antibodies in 5/9 (56%) adult RA patients and in 8/34 (24%) SLE patients. No healthy control had elevated anti-CCP antibodies. However, the Axis-Shield kits did not detect anti-CCP antibodies in adult RA (0/9) or SLE (0/34) patients. Moreover, 0/25 (0%) healthy individuals exhibited anti-CCP levels. The presence of anti-CCP antibodies correlated more frequently with the presence of RF. Conclusion. This study confirms the presence of anti-CCP antibodies in patients with JIA, especially those with RF positive polyarthritis, by all ELISA based methods. Use of synthetic peptides also revealed anti-CCP antibodies in a percentage of RF negative patients with polyarthritis, oligoarthritis, and systemic arthritis; there was a loss in specificity, but an increase in sensitivity. These results suggest that antibodies to these antigenic peptides may be markers for JIA, and indicate a possible role of citrulline-containing epitopes in the pathogenesis of JIA

19. METIN G, OZTURK L, KASAPCOPUR O, APELYAN M, ARISOY N: Cardiopulmonary exercise testing in juvenile idiopathic arthritis. Journal of Rheumatology (Canada ) 31:9 1834-1839, 2004
    Abstract: Objective. To assess aerobic fitness and exercise capacity in patients with juvenile idiopathic arthritis (JIA) and to determine subgroup differences. Methods. Thirty-four patients diagnosed with JIA and 21 healthy sedentary volunteers were studied. Aerobic fitness was determined by measuring peak power and peak oxygen uptake (VOSUB2peak) during an incremental cycling test. The patient group consisted of systemic JIA (n = 8), polyarticular JIA (n = 13), oligoarticular JIA (n = 7), and enthesitis-related arthritis (ERA, n = 6). Results from different subgroups of JIA were compared to determine subgroup differences. Results. All subjects tolerated maximal exercise testing well. The JIA group had lower aerobic fitness than controls. In our comparison of JIA subgroups, we found no significant differences in cardiopulmonary measures. The ERA group had higher aerobic capacity than other subgroups. There was no difference in exercise capacity between patients with active disease (n = 10) and those in remission (n = 24). Conclusion. We suggest that heterogeneity in VOSUB2peak levels among JIA patients is due to subgroup differences. Exercise programs for improvement of aerobic fitness should be individualized or at least be modified according to different subgroups

20. MYERS A, MCDONAGH JE, GUPTA K, HULL R, BARKER D, KAY LJ, FOSTER HE: More 'cries from the joints': Assessment of the musculoskeletal system is poorly documented in routine paediatric clerking. Rheumatology (United Kingdom ) 43:8 1045-1049, 2004
    Abstract: Objectives. The aim of this study was to describe the assessment of the musculoskeletal (MSK) system in comparison with other systems in routine paediatric medical clerking. Furthermore, to survey trainee paediatricians (SPRs, specialist registrars) about their self-rated confidence in assessing the MSK system. Methods. Case notes of consecutive general paediatric medical patients admitted to three UK hospitals over a 4-week period were assessed using a standard pro forma. All patients had been assessed by a consultant paediatrician during their admission. A postal questionnaire was sent to all SPRs in training in each of the hospitals, regarding their confidence in assessing the MSK system compared with other systems and their exposure to MSK teaching. Results. Case notes of 257 patients [117 females, median age 3 yr (range 1-18 yr)] were reviewed. The most common reason for admission was acute infection, although the spectrum of other recorded diagnoses varied between hospitals. Thirteen children (5%) had an acute problem (e.g. infection) against a background of chronic disease. The case note documentation showed that cardiovascular (CVS), respiratory (RS) and gastrointestinal (GI) systems were assessed in the vast majority (> 90%) of patients, irrespective of the underlying diagnosis. However, other systems were less well recorded; the trend being the same in each hospital and in descending order, the neurological system (38%), skin (32%), eyes (10%) and musculoskeletal system (4%). Only 2.7% (7/257) patients were documented to have been asked about MSK symptoms, and only 1.6% (4/257) had any documentation of joint examination - in all cases this was limited (e.g. range of movement of the knee only), and no patients had documentation of gait being examined, even in those children presenting with 'limp'. The response rate to the postal questionnaire was 60% (67/112). The self-rated confidence in MSK assessment was markedly low, in comparison with other systems, even though 61/67 recalled some teaching of the MSK system as an undergraduate (61/67) or postgraduate (50/67). of note none could recall teaching as an undergraduate in paediatric MSK assessment and where there had been postgraduate rheumatology MSK teaching this had been delivered by paediatric rheumatologists in many cases (34/50), reflecting the centres participating in the study. Conclusions. In routine general paediatric medical in-patient clerking and throughout the admission, MSK assessment was rarely documented, and even where present was limited. This contrasts markedly with other systems which were examined in most children irrespective of the presenting complaint. Self-rated confidence in MSK assessment is low amongst SPRs compared with other systems, despite most recalling some teaching. This discrepancy between teaching and clinical practice needs to be addressed in undergraduate and postgraduate training. (c) British Society for Rheumatology 2004; all rights reserved

21. PADMINI A, USHASREE B, BABU R, PRATIBHA N: Association of alkaline phosphatase phenotypes with arthritides. Indian Journal of Human Genetics (India ) 10:1 5-8, 2004
    Abstract: Arthritides, a symmetrical polyarticular disease of the bone am a heterogenous group of disorders in which hereditary and environmental factors in combination with an altered immune response appear to play a causative and pathogenic role in its occurrence. Alkaline phosphatase (ALP) is an enzyme found in all tissues, with particularly high concentrations of ALP observed in the liver, bile ducts, placenta, and bone.Alkaline phosphatase is an orthophosphoric monoester phosphohydrolase catalyzing the hydrolysis of organic esters at alkaline pH, indicating that alkaline phosphatase is involved in fundamental biological processes. SUP1 The present study envisages on identifying the specific electromorphic association of alkaline phosphatase with arthritides. Phenotyping of serum samples was carried out by PAGE (Polyacrylamide gel electrophoresis) following Davies (1964 SUP2 protocol on 41 juvenile arthritis, 150 rheumatoid arthritis and 100 osteo arthritis apart from, 25 normal children and 100 adult healthy subjects. Phenotyping of alkaline phosphatase revealed an increase in preponderance of p+ and p++ phenotypes in juvenile, rheumatoid and osteo arthritic patients. However a significant association of these phenotypes was observed only with rheumatoid arthritis condition (cSUP2:17.46). Similarly, a significant increase of p+ phenotypes in female rheumatoid arthritis patients was observed (cSUP2:14.973), suggesting that the decrease in pSUPo (tissue non specific) synthesis/secretion of alkaline phosphatase could be associated with decreased mineralization and ossification process in arthritis condition

22. PALERMO TM, ZEBRACKI K, COX S, NEWMAN AJ, SINGER NG: Juvenile idiopathic arthritis: Parent-child discrepancy on reports of pain and disability. Journal of Rheumatology (Canada ) 31:9 1840-1846, 2004
    Abstract: Objective. To examine the incidence and nature of disagreements about pain and functional disability between parents and their children with juvenile idiopathic arthritis (JIA) and to identify demographic and psychosocial predictors of parent-child disagreement about pain and functional disability. Methods. Participants comprised 63 children 8-16 years of age (mean 12.36 +/- 2.61) and their parents, followed as part of a longitudinal study of pain in children. During routine rheumatology clinic visits, children and their parents completed validated measures of pain, depressive symptoms, and functional disability. Results. Parents and children often disagreed as to the frequency and intensity of pain and to the degree of disability caused by arthritis. Child depressive symptoms (p < 0.01) and parental perceptions of child limitations (p < 0.02) predicted parent-child disagreement about the frequency of the child's pain. Parental perceptions of child limitations also predicted parent-child disagreement about the child's level of functional disability (p < 0.04). Those children who estimated their level of disability to be different than their parents' rating also were more depressed compared to children who agreed with their parents about their level of disability (p < 0.01). Conclusion. Discrepancy between parent and child reports of pain and disability in children with JIA is common. Findings suggest that such disagreements in reporting of pain and functional disability by parents and their children with JIA are associated with underlying depressive symptoms in children

23. RUEMMELE FA, PRIEUR A-M, TALBOTEC C, GOULET O, SCHMITZ J: Development of Crohn disease during anti-TNF-alpha therapy in a child with juvenile idiopathic arthritis. JPGN Journal of Pediatric Gastroenterology and Nutrition 39:2 203-206, 2004

24. RUNSTADLER JA, SAILA H, SAVOLAINEN A, LEIRISALO-REPO M, AHO K, TUOMILEHTO-WOLF E, TUOMILEHTO J, SELDIN MF: HLA-DRB1, TAP2/TAP1, and HLA-DPB1 haplotypes in Finnish juvenile idiopathic arthritis: more complexity within the MHC. Genes Immun .: 2004
    Organism: 1Rowe Program in Human Genetics and Molecular Medicine, Departments of Biological Chemistry and Medicine, University of California, Davis, USA
    Abstract: This study further defines genetic susceptibility to JIA in the region centromeric to HLA-DRB1. DNA from 234 Finnish JIA nuclear families and 639 elderly Finnish control individuals was genotyped for five functional SNPs within the TAP2 and TAP1 loci ( approximately 200 kb centromeric of HLA-DRB1). Subsets of the controls (186) and patients (145) that had been previously typed for HLA-DRB1 were also genotyped by sequence for the HLA-DPB1 locus. Case/control and transmission disequilibrium test (TDT) methods revealed an association with the DPB1(*)030101 allele for JIA (OR 2.3, 95% CI 1.5-3.5). Notably, a detailed haplotypic analysis of the TAP2/TAP1 loci and their interaction with the HLA-DPB1(*)030101 and DRB1(*)08 and (*)11 alleles showed a variety of over-represented and under-represented TAP2/TAP1 haplotypes not evident in the single marker analysis. The strongest effect was observed in the polyarticular RF negative JIA subgroup for the 2-2-1-2-1 TAP2/TAP1 haplotype (TAP2B and TAP1A alleles) which showed an independent effect from both DRB1(*)08 and (*)11 (P<0.000003) and DPB1(*)030101 (P=0.02). We have provided evidence that the extended haplotypes (including HLA-DRB1, TAP2/TAP1, and HLA-DPB1) of pauciarticular and polyarticular RF negative disease are distinct. This observation may have implications for functional etiological differences between the pauciarticular and polyarticular JIA patients.Genes and Immunity advance online publication, 2 September 2004; doi:10.1038/sj.gene.6364129

25. SCHIKLER KN: Growth hormone therapy in juvenile arthritis: importance of classification. J Pediatr 145:3 423-424, 2004

26. SOBEK V, BIRKNER N, FALK I, WURCH A, KIRSCHNING CJ, WAGNER H, WALLICH R, LAMERS MC, SIMON MM: Direct Toll-like receptor 2 mediated co-stimulation of T cells in the mouse system as a basis for chronic inflammatory joint disease. Arthritis Res Ther 1919
    Organism: Department of Cellular Immunology, Max-Planck-Institut fur Immunbiologie, Freiburg, Germany simon@immunbiompgdeFAU - Sobek, Vera
    Abstract: The pathogenesis of chronic inflammatory joint diseases such as adult and juvenile rheumatoid arthritis and Lyme arthritis is still poorly understood. Central to the various hypotheses in this respect is the notable involvement of T and B cells. Here we develop the premise that the nominal antigen-independent, polyclonal activation of preactivated T cells via Toll-like receptor (TLR)-2 has a pivotal role in the initiation and perpetuation of pathogen-induced chronic inflammatory joint disease. We support this with the following evidence. Both naive and effector T cells express TLR-2. A prototypic lipoprotein, Lip-OspA, from the etiological agent of Lyme disease, namely Borrelia burgdorferi, but not its delipidated form or lipopolysaccharide, was able to provide direct antigen-nonspecific co-stimulatory signals to both antigen-sensitized naive T cells and cytotoxic T lymphocyte (CTL) lines via TLR-2. Lip-OspA induced the proliferation and interferon (IFN)-gamma secretion of purified, anti-CD3-sensitized, naive T cells from C57BL/6 mice but not from TLR-2-deficient mice. Induction of proliferation and IFN-gamma secretion of CTL lines by Lip-OspA was independent of T cell receptor (TCR) engagement but was considerably enhanced after suboptimal TCR activation and was inhibitable by monoclonal antibodies against TLR-2

27. TAGIL M, REIMERTZ J, ELBORGH R, KOPYLOV PHILIPPE: Intravenous regional administration of corticosteroids in juvenile chronic arthritis. Acta Orthop Scand 75:3 352-354, 2004
    Abstract: Background Treatment of juvenile chronic arthritis patients with longstanding multiple joint or tendon involvement that is resistant to medication remains a challenge. For 20 years, we have been treating these severely ill patients with intravenous regional glucocorticoids (a modified Bier's block). Patients and methods Since 1996, all juvenile chronic arthritis patients have been followed prospectively by an occupational therapist who has registered the grip strength and range of motion at an average of 6 months after treatment. Results In 22/40 wrists and hands, increased grip strength was recorded. The mean grip strength increased for the whole group from 47 to 59 N and the flexion lag decreased. Interpretation The effect of intravenous regional steroid treatment may be limited from a long-term perspective, but in our series, half of the patients showed a considerable improvement after 6 months. Surgical synovectomy can be postponed and perhaps even be omitted

28. THOMPSON SD, MOROLDO MB, GUYER L, RYAN M, TOMBRAGEL EM, SHEAR ES, PRAHALAD S, SUDMAN M, KEDDACHE MA, BROWN WM, GIANNINI EH, LANGEFELD CD, RICH SS, NICHOLS WC, GLASS DN: A genome-wide scan for juvenile rheumatoid arthritis in affected sibpair families provides evidence of linkage. Arthritis and Rheumatism (United States ) 50:9 2920-2930, 2004
    Abstract: Objective. Juvenile rheumatoid arthritis (JRA) represents a heterogeneous group of disorders with a complex genetic component. A genome scan was performed to detect linkage to JRA in 121 families containing 247 affected children in North America (the JMA Affected Sibpair [ASP] Registry). Methods. Genotype data collected for HLA-DR and 386 microsatellite markers were subjected to multipoint nonparametric linkage analysis. Following analysis of the entire set of families, additional analyses were performed after a priori stratification by disease onset type, age at onset, disease course, and selected HLA-DRB1 alleles. Results. Linkage of JRA to the HLA region was confirmed (logarithm of odds [LOD] score 2.26). Additional evidence supporting linkage of JRA was observed at 1p36 (D1S214; LOD 1.65), 19p13 (D19S216; LOD 1.72), and 20q13 (D20S100; LOD 1.75). For early-onset polyarticular disease, evidence of linkage was found at chromosome 7q11 (D7S502; LOD 3.47). For pauci-articular disease, evidence supporting linkage was observed on chromosome 19p13 (D19S216; LOD 2.98), the same marker that supported linkage to the "JRA" phenotype. Other regions supporting linkage with JRA disease subtype included 20q13, 4q24,12q24, and Xp11. Stratification of families based on the presence of the HLA-DR8 allele in affected siblings resulted in significant linkage observed at 2p25 (D2S162/D2S305; LOD 6.0). Conclusion. These data support the hypothesis that multiple genes, including at least 1 in the HLA region, influence susceptibility to JRA. These findings for JRA are consistent with findings for other autoimmune diseases and support the notion that common genetic regions contribute to an autoimmune phenotype

29. WULFFRAAT NM, DE KLEER IM, PRAKKEN BJ, KUIS W: Refractory juvenile idiopathic arthritis. Best Practice and Research in Clinical Haematology (United Kingdom ) 17:2 277-289, 2004
    Abstract: Since 1997, haematopoietic stem cell transplantation (HSCT) has been applied as an experimental procedure in more than 50 children with refractory juvenile idiopathic arthritis. We describe here follow-up data on 34 children with juvenile idiopathic arthritis, treated with HSCT in order to evaluate its feasibility, safety and efficacy. Data were collected on immunological reconstitution, complications and key rheumatological parameters. The clinical follow-up of the children ranged from 12 to 48 months. Eighteen of the 34 patients achieved a drug-free complete remission. Seven of these patients had previously failed treatment with anti-tumour necrosis factor-alpha. Six of the 34 patients showed a partial response (ranging from 30 to 70%), and 7 of the 34 patients showed a complete relapse of disease. Infectious complications were frequently seen. There were three cases of transplant-related mortality and two cases of disease-related mortality. It is still unclear why especially patients with systemic juvenile idiopathic arthritis are at risk of episodes of reactive haemophagocytosis. (c) 2004 Elsevier Ltd. All rights reserved