Bibliography February 04

1. DUFFY CM: Health outcomes in pediatric rheumatic diseases. Curr Opin Rheumatol 16:2 102-108, 2004
   Abstract: SUMMARY: PURPOSE OF REVIEW Health outcomes in the pediatric rheumatic diseases have been a very active area of research in the past several years, with a significant number of published studies from the United States, Canada, and Europe. Although most studies have been in the area of juvenile idiopathic arthritis, there are increasing numbers of studies in juvenile dermatomyositis and juvenile systemic lupus erythematosus.RECENT FINDINGS These studies suggest that although there has been an improvement in overall outcomes, active disease persists in significant proportions of individuals into adulthood, causing damage and disability. In juvenile idiopathic arthritis, this is particularly so for patients with systemic arthritis and polyarthritis with rheumatoid factor positivity who overall appear to have a poor prognosis.SUMMARY With the current approach to treatment of all these diseases being more aggressive, one anticipates an improvement in these outcomes in the future. Better longitudinal outcome studies with larger inception cohorts of new-onset disease are required to ascertain whether this prediction can be upheld. Such studies are now ongoing

2. EHL S, UHL M, BERNER R, BONAFE L, SUPERTI-FURGA A, KIRCHHOFF A: Clinical, radiographic, and genetic diagnosis of progressive pseudorheumatoid dysplasia in a patient with severe polyarthropathy. Rheumatology International (Germany ) 24:1 53-56, 2004
   Abstract: A 14-year-old boy presented with a 10-year history of the "sicca" form of seronegative juvenile idiopathic polyarthritis. Severely limited range of motion, pain, and capsular swelling in both small and large weight-bearing joints left him wheelchair-bound. Erythrocyte sedimentation rate and C-reactive protein were normal. Two-phase bone scan revealed tracer uptake of almost every joint at both early and late time points, indicating pathologic exudation and enhanced bone metabolism consistent with severe arthritis. However, radiographic studies revealed no erosive arthropathy but severe osteopenia, dysplastic bone changes, mega os trigonum, and platyspondylia. A magnetic resonance imaging (MRI) scan of the hips showed no signs of synovitis, pannus, or effusion but cartilage irregularities and subchondral cysts. These findings strongly suggested the diagnosis of progressive pseudorheumatoid dysplasia of childhood, an autosomalrecessive disorder of cartilage homeostasis. The patient carries a novel homozygous two-nucleotide deletion in exon 4 of the WISP3 gene. This genetic disorder is an important differential diagnosis of sicca polyarthritis

3. FRIERI M: Identification of masqueraders of autoimmune disease in the office. Allergy Asthma Proc 24:6 421-429, 2003
   Organism: Department of Medicine, Pediatrics and Pathology, Nassau University Medical Center, 2201 Hempstead Turnpike, East Meadow, NY 11554, USAFAU - Frieri, Marianne
   Abstract: There are several rheumatologic and autoimmune disorders that can masquerade as allergic disease. Identification of these conditions in an office setting can be a challenge for the practicing allergist-immunologist. These conditions include rheumatoid and juvenile arthritis, Sjogren's syndrome, systemic lupus erythematosus, Behcet's and antiphospholipid syndromes, systemic sclerosis, vasculitis, sarcoidosis, chronic fatigue syndrome, and fibromyalgia. The article will address these topics and include clinical uses of immunologic tests for diagnosis

4. GONZALEZ QS, SEVIL PM, VALLEDOR AR, LOMA R: [Clinical analysis of 91 cases of median and small vessel vasculitis in adults]. An Med Interna 20:9 461-465, 2003
   Organism: Seccion de Medicina Interna, 8a planta, Hospital General Yague, Avda Cid Campeador, 96, 09005 BurgosFAU - Gonzalez Quijada, S
   Abstract: OBJECTIVE: To evaluate the clinical and biological differences between medium sized vessel vasculitis and small vessel vasculitis. PATIENTS AND METHODS: descriptive and retrospective study of 91 patients with vasculitis attended in our hospital from January 1991 to mars 2001. We describe the characteristics of clinical and analytic features. RESULTS: 57% were males. The mean age was 61.9 +/- 18.6 years (17 to 90 years). The symptoms and affected organs were: palpable purpura (89%), fever (36%), asthenia (20%), arthromyalgias (19%), nephropathy (18%), arthritis (16%), abdominal pain (16%), neuropathy (8.7%), pulmonary involvement (6.5%). 25% had several episodes, lasting clinical, chronic disease, 42% had evidence of two or more involve organs. The patients with pauci-inmune vasculitis presented more asthenia, nephritis, pulmonary involvement, multi-organic involvement and mortality related to the process. We did not found significant differences respect to the others clinical manifestations analysed. CONCLUSIONS: There is a substantial overlap among different vasculitis, the presence or absence of some clinical and biological features can help in the differentiation and characterization of the different entitles

5. INGEGNOLI F, DEL PAPA N, LUPI E, COMINA DP, MAGLIONE W, GERLONI V, FANTINI F: [Anti-chromatin antibodies in juvenile rheumatoid arthritis]. Reumatismo 55:4 240-244, 2003
   Organism: Cattedra di Reumatologia, Istituto Gaetano Pini, Milano, Italia francescaingegnoli@yahoocomFAU - Ingegnoli, F
   Abstract: OBJECTIVE: to evaluate the prevalence and clinical significance of anti-chromatin antibodies (Abs) in juvenile rheumatoid arthritis (JRA). METHODS: IgG anti-chromatin Abs were detected by an enzyme-linked immunosorbent assay (ELISA), in sera of 94 children with JRA (10 children with systemic, 38 with polyarticular and 46 with oligoarticular disease onset). As control group, 33 age- and-sex-matched healthy children (HC) were also examined. RESULTS: Abs to chromatin were detected in 24/94 (25.5%) of children suffering from JRA. Particularly, the higher prevalence of anti-chromatin Abs has been found in children with oligoarticular (30,4%) and polyarticular (23.7%) onset JRA. In these groups Abs titers were significantly higher compared to systemic JRA and HC (p=0.003). Anti-chromatin Abs were observed more frequently in patients with oligoarticular disease and chronic uveitis (21.7%). Furthermore, higher levels of anti-chromatin Abs has been found in all the patients treated with anti-TNF-alpha therapy (p< 0.0001). CONCLUSIONS: our results confirm previous data about the prevalence of anti-chromatin Abs in JRA. These Abs were significantly higher in the group of patients with oligoarticular onset with past or present history of ocular involvement and in the group with polyarticular JRA treated with biologic therapy. A long-term follow-up study could be useful to evaluate the potential utility of these autoantibodies

6. IQBAL MP, AHMED M, UMER M, MEHBOOBALI N, QURESHI AA: Effect of methotrexate and folinic acid on skeletal growth in mice. Acta Paediatr 92:12 1438-1444, 2003
   Organism: Department of Biological & Biomedical Sciences, The Aga Khan University, Karachi, Pakistan perwaiziqbal@akueduFAU - Iqbal, M P
   Abstract: AIM: To investigate whether chronic administration of medium doses of methotrexate (MTX) causes suppression of skeletal growth in young mice and to determine whether folinic acid supplementation could reverse this effect. METHODS: Four equal groups of Balb/c young male mice (6 animals in each group; mean body weight 11.9 +/- 0.25 g, in their rapid growth phase) were subjected to the following drug treatment for a period of 3 wk. Group 1 was given intraperitoneal MTX (3.5 mg kg(-1) body weight) every second day. Group 2 received folinic acid (7.0 mg kg(-1) body weight) intraperitoneally every second day. Group 3 was given both drugs (MTX every second day and folinic acid 8 h post-MTX injection). Group 4 was injected with physiological saline every other day to serve as a control group. Total body weight of the animals in each group was monitored every second day for the entire study period. The animals were sacrificed, the bilateral femurs and tibias of each animal were harvested and X-rays of the bones were taken. The length of each femur and tibia was measured using a micrometer. Measurements from the radiographs were also recorded using image analysis software. The MTX concentrations in the plasma and the folate levels in erythrocytes were determined. The heights of the distal femoral and the proximal tibial growth plate for each animal were measured on histological tissue sections. RESULTS: Mean lengths of both the tibia and femur of animals were compared in the four treatment groups. A significant decrease in the mean lengths (one-way ANOVA, p < 0.005) was observed in the group receiving MTX alone. Similarly, there was a significant decrease (p < 0.001) in the height of the femoral and tibial growth plate in this group when compared with the other groups. The main effect of MTX seemed to be on the hypertrophic proliferative zone of chondrocytes in the growth plate. Furthermore, animals in this MTX-treated group also showed increased levels of MTX in plasma and low levels of erythrocyte folate. CONCLUSION: These data show that chronic administration of MTX induces suppression of skeletal growth in mice, possibly through the inhibition of the pathway of de novo DNA synthesis. Folinic acid treatment following MTX administration appears to reverse this growth inhibition. Based on these observations, children suffering from juvenile rheumatoid arthritis, osteosarcoma or acute lymphoblastic leukaemia and receiving MTX over long periods of time could be at risk of short-term suppression of skeletal growth. If this is the case, it is possible that they could benefit from dietary supplementation with folinic acid

7. JARVIS JN, DOZMOROV I, JIANG K, FRANK MB, SZODORAY P, ALEX P, CENTOLA M: Novel approaches to gene expression analysis of active polyarticular juvenile rheumatoid arthritis. Arthritis Res Ther 6:1 R15-R32, 2004
   Organism: Department of Pediatrics, University of Oklahoma College of Medicine, Oklahoma City, OK, USA james-jarvis@ouhscedu
   Abstract: Juvenile rheumatoid arthritis (JRA) has a complex, poorly characterized pathophysiology. Modeling of transcriptosome behavior in pathologic specimens using microarrays allows molecular dissection of complex autoimmune diseases. However, conventional analyses rely on identifying statistically significant differences in gene expression distributions between patients and controls. Since the principal aspects of disease pathophysiology vary significantly among patients, these analyses are biased. Genes with highly variable expression, those most likely to regulate and affect pathologic processes, are excluded from selection, as their distribution among healthy and affected individuals may overlap significantly. Here we describe a novel method for analyzing microarray data that assesses statistically significant changes in gene behavior at the population level. This method was applied to expression profiles of peripheral blood leukocytes from a group of children with polyarticular JRA and healthy control subjects. Results from this method are compared with those from a conventional analysis of differential gene expression and shown to identify discrete subsets of functionally related genes relevant to disease pathophysiology. These results reveal the complex action of the innate and adaptive immune responses in patients and specifically underscore the role of IFN-gamma in disease pathophysiology. Discriminant function analysis of data from a cohort of patients treated with conventional therapy identified additional subsets of functionally related genes; the results may predict treatment outcomes. While data from only 9 patients and 12 healthy controls was used, this preliminary investigation of the inflammatory genomics of JRA illustrates the significant potential of utilizing complementary sets of bioinformatics tools to maximize the clinical relevance of microarray data from patients with autoimmune disease, even in small cohorts

8. KISHIMOTO T, HAMAZAKI T, YASUI M, SASABE MAKOTO, OKAMURA T, SAKATA N, INOUE M, YAGI K, KAWA KEISEI_(REPRINT): Autologous hematopoietic stem cell transplantation for 3 patients with severe juvenile rheumatoid arthritis. Int J Hematol 78:5 453-456, 2003
   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

9. KVIEN TK, UHLIG T: The Oslo experience with arthritis registries. Clin Exp Rheumatol 21:5 Suppl 31 S118-S122, 2003
   Organism: Oslo City Department of Rheumatology, Diakonhjemmet Hospital, Oslo, Norway tkkvien@ioksuionoFAU - Kvien, T K
   Abstract: The Oslo experience with early rheumatoid arthritis (RA) is based on studies performed within the setting of a register of RA patients and of the longitudinal follow-up of patients with early RA. This article discusses some relevant issues for research on early arthritis: whether the current RA classification criteria are appropriate, the shift in incidence toward elderly patients, and the heterogeneity of the disease. Our data clearly show that 3 of the items of the classification criteria are infrequently fulfilled early in the disease and that RA most frequently starts after the age of 60. Our data also suggest that disease onset may be defined either as symptom onset or as when the classification criteria are fulfilled. The choice between these 2 options does not seem to influence the longitudinal results

10. LYBACK CO, BELT EA, SAVOLAINEN HA, LEHTINEN JT, LYBACK CC, LEHTO MU: Previous synovectomy or epiphyseal stapling and the influence on knee replacement in juvenile chronic arthritis. Int Orthop .: 2004
    Organism: Porvoo District Hospital, Porvoo, Finland
    Abstract: Seventy-seven anatomically graduated components (AGC) total knee arthroplasties (TKA) were performed on 52 patients with juvenile chronic arthritis. According to the nature of previous surgery on the knee, the patients were subdivided into three groups. The mean age at onset of disease in 23 patients with previous synovectomy of the knee was 11 (1.5-16) years, the mean age at the time of synovectomy was 20 (4-42) and the mean age when arthroplasty was performed was 31 (18-45) years. In nine patients with previous epiphyseal stapling, the mean age at disease onset was 4 (1.5-8) years, at stapling 8 (4-16) years, and at arthroplasty 23 (18-30) years. In patients with no previous surgery, the mean age at disease onset in this group was 7 (1.5-16) years and the mean age at arthroplasty 34 (16-64) years. Patients with need for epiphyseal arrest had an early disease onset and knee replacement in early adulthood. The mean age at knee replacements was highest in the group with no prior surgery

11. MACHOLD KP, NELL VP, STAMM TA, EBERL G, STEINER G, SMOLEN JS: The Austrian Early Arthritis Registry. Clin Exp Rheumatol 21:5 Suppl 31 S113-S117, 2003
    Organism: Division of Rheumatology, Department of Internal Medicine III, University of Vienna, AustriaFAU - Machold, K P
    Abstract: The Austrian Early Arthritis Registry (Austrian Early Arthritis Action, EAA) enrols and follows patients with inflammatory arthritis of very short (< 12 weeks) duration. Currently, data on 375 patients (almost 2000 individual follow-up examinations) have been entered into the EA database. Evaluations of data from 182 patients with a follow-up of at least one year are available. 65% of these patients have RA, as diagnosed using the ACR classification criteria in a cumulative fashion. Approximately 15% of these patients still have no established diagnosis and are being carried forward and observed as cases of "undifferentiated arthritis". In RA patients, the mean DAS 28 decreased significantly from an initial mean score of 5.5 (high disease activity) into the range of low disease activity. At the end of one year a DAS 28 of < 3.2 was observed in 52% of the RA patients. Radiological progression in these RA patients, who also received treatment very early, appears to be less severe than in other cohorts, although direct comparisons are impossible due to different methods of patient selection. In addition, the serological data from our cohort in cooperation with other study groups will allow development and validation of possible prediction algorithms for early arthritis patients which could improve the diagnostic and therapeutic approach to this patient group

12. MADI SM, AL MAYOUF SM, GRAINGER CG, BAHABRI SA: The Arabic version of childhood health assessment questionnaire modified for Arabic children. Saudi Med J 25:1 83-87, 2004
    Organism: Senior Pediatric Physical Therapist, Department of Physical Therapy, MBC 45, King Faisal Specialist Hospital and Research Centre, PO Box 3354, Riyadh, 11211, Kingdom of Saudi Arabia Tel +966 (1) 4423893/4424709 Fax +966 (1) 4423897 E-mail: sanamadi@hotmailcom
    Abstract: OBJECTIVE: To determine the feasibility, reliability and validity of the childhood health assessment questionnaire - modified for Arab children (CHAQ- MAC). METHODS: One hundred and eighteen modified questionnaires were completed by 75 juvenile rheumatoid arthritis (JRA) patients and their parents attending the Pediatric Rheumatology Clinic at the King Faisal Specialist Hospital and Research Centre, Riyadh, Kingdom of Saudi Arabia over an 18 month period (January 1996 to May 1997). RESULTS: The modified questionnaire was self-administered by 82% of the parents. The median time to complete the questionnaire was 10 minutes. The main difficulty in comprehension was discomfort dimension (visual analogue scale [VAS] and morning stiffness). Test retest reliability was good (r=0.79). Validity of the CHAQ-MAC was confirmed by the strong correlation between disability index and VAS score (r=0.58). Functional activities that caused the most difficulties were cross sitting, assuming the prayer position, and using the Arabic style toilet. CONCLUSION: The modified CHAQ is a suitable assessment tool for Arab children suffering from JRA

13. MANGGE H, HEINZL B, GRUBBAUER H-M, ASCHAUER M, TILLICH M: Fatal Occlusive Vessel Disease in a Patient with Systemic Juvenile Idiopathic Arthritis. Journal of Rheumatology (Canada ) 31:2 396, 2004

14. MIRANDA LA, FISCHER RG, SZTAJNBOK FR, FIGUEREDO CM, GUSTAFSSON A: Periodontal conditions in patients with juvenile idiopathic arthritis. J Clin Periodontol 30:11 969-974, 2003
    Organism: Division of Periodontology, Institute of Odontology, Karolinska Institutet, Huddinge, Sweden leticiamiranda@ofakiseFAU - Miranda, Leticia A
    Abstract: OBJECTIVE: Our aim was to compare the periodontal conditions in a group of juvenile idiopathic arthritis (JIA) patients with those in a control group of healthy subjects (CTR). MATERIAL AND METHODS: Thirty-two patients with JIA and 24 controls were selected. The measurements used to diagnose periodontal disease included plaque and bleeding scores, probing depths (PDs) and clinical attachment loss (CAL). Laboratory indicators of JIA activity included the erythrocyte sedimentation rate (ESR) and capsule-reactive protein (CRP). The Mann-Whitney test was used to evaluate the data (alpha = 0.05). RESULTS: The mean ages were 15.9 (+/- 2.7) years and 14.7 (+/- 2.3) years for groups JIA and CTR, respectively. The median ESR was 42 mm/h 13 mm/h in the CTR group (p = 0.032) and the median CRP was 1.9 and 0.4 mg/l, respectively (p = 0.001). The prevalence of patients with a proximal attachment loss of 2mm or more in the JIA group was 25% and in controls it was 4.2%. The mean percentages of visible plaque and marginal bleeding were similar in the JIA (54 +/- 22 and 30 +/- 16, respectively) and CTR groups (44 +/- 18 and 29 +/- 11, respectively). The mean percentages of sites with PD > or = 4 mm were significantly higher in the JIA group (3 +/- 4.7) than in the CTR group (0.4 +/- 1.7) (p = 0.012). The mean percentages of sites with proximal CAL > or = 2 mm were 0.7 (+/- 1.4) in the JIA group and 0.001 (+/- 0.2) in the CTR group (p = 0.022). CONCLUSION: Adolescents with JIA present more periodontal attachment loss than healthy controls, in spite of similar plaque and marginal bleeding levels

15. OKAMOTO Y, GOTOH Y, SHIRAISHI H, NISHIDA M: A human dual-color enzyme-linked immunospot assay for simultaneous detection of interleukin 2- and interleukin 4-secreting cells. Int Immunopharmacol 4:1 149-156, 2004
    Organism: Division of Health Care Pharmacy, Faculty of Pharmacy, Meijo University, 150 Yagotoyama, Tempaku-ku, Nagoya 468-8503, JapanFAU - Okamoto, Y
    Abstract: The enzyme-linked immunospot (ELISPOT) assay is an efficient technique for the enumeration of single cells secreting antibodies and cytokines. For simultaneous differentiation of individual cells producing interleukin-2 (IL-2) and interleukin-4 (IL-4) at a single cell level in human peripheral blood mononuclear cells (PBMCs), a human dual-color ELISPOT assay has been optimized. In the present system, the red spots corresponding to IL-2-secreting cells (T helper type 1, Th1, cells) were developed with horseradish peroxidase and the amino ethyl carbazole (AEC)/H(2)O(2). The blue spots corresponding to IL-4-secreting cells (T helper type 2, Th2, cells) were developed with an alkaline phosphatase and the Vector blue. The usefulness of the assay method was tested. With this system, we could detect the IL-2- and IL-4-secreting cells simultaneously in human PBMCs of a juvenile rheumatoid arthritis (JRA) patient. This procedure provides useful information on clinical immune disorders

16. OLGUIN HJ, PEREZ JF, ASSEFF IL, ABDALA AL, RODRIGUEZ LC: Comparative pharmacokinetics of acetyl salicylic acid and its metabolites in children suffering from autoimmune diseases. Biopharmaceutics and Drug Disposition (United Kingdom ) 25:1 1-7, 2004
    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 24h 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. Copyright (c) 2004 John Wiley & Sons, Ltd

17. PETTY RE, SOUTHWOOD TR, MANNERS P, BAUM J, GLASS DN, GOLDENBERG J, HE X, MALDONADO-COCCO J, OROZCO-ALCALA J, PRIEUR A-M, SUAREZ-ALMAZOR ME, WOO P: International League of Associations for Rheumatology Classification of Juvenile Idiopathic Arthritis: Second Revision, Edmonton, 2001. Journal of Rheumatology (Canada ) 31:2 390-392, 2004

18. RAVELLI A, MARTINI A: Early predictors of outcome in juvenile idiopathic arthritis. Clin Exp Rheumatol 21:5 Suppl 31 S89-S93, 2003
    Organism: Dipartimento di Pediatria, Universita di Genova, UO Pediatria II, IRCCS G Gaslini, Genova, Italy angeloravelli@ospedale-gaslinigeitFAU - Ravelli, A
    Abstract: The definition and management of "early arthritis" in children differ from those in adults because juvenile idiopathic arthritis (JIA) is markedly different from adult rheumatoid arthritis. Since a significant proportion of patients with JIA develop articular damage and enter adult life with persistently active disease, it is important to predict early in the disease course the long-term outcome in order to tailor treatment to the risk of disability. Over the past 3 decades a number of studies have evaluated the long-term outcome of cohorts of patients with JIA and some of them have also attempted to identify early prognostic factors. In summary, greater severity/extension of arthritis at onset, symmetric disease, precocious hip/wrist involvement, the presence of rheumatoid factor, and prolonged active disease were the best predictors of a poor outcome. Specific correlates for systemic JIA were persistent systemic features and thrombocytosis at 6 months following presentation, whereas joint symmetry and a higher erythrocyte sedimentation rate at onset were associated with a more severe course in oligoarticular JIA. However, although data is accumulating on prognostic factors in JIA, prediction of long-term outcome in the first few months remains difficult. To better define prognostic factors in future analyses, a considerable effort should be made to increase standardization among studies. Furthermore, a radiographic scoring system and a set of remission criteria specific for JIA should be developed

19. SAUER ST, FARRELL E, GELLER E, PIZZUTILLO PD: Septic Arthritis in a Patient with Juvenile Rheumatoid Arthritis. Clinical Orthopaedics and Related Research (United States ) -:418 219-221, 2004
    Abstract: The acute flare of joint inflammation in the child with known juvenile rheumatoid arthritis causes concern primarily regarding the need for additional or modified medical treatment. Acute joint inflammation in an otherwise healthy child creates concern regarding the existence of joint infection. In the early phase of disease, the clinical findings and symptoms of an inflamed joint attributable to juvenile rheumatoid arthritis or infection may be similar and difficult to differentiate from the other. Juvenile rheumatoid arthritis usually is well controlled by medical interventions, however, the initiation of specific treatment is more urgent in children with joint sepsis. The following case report is presented to emphasize the difficulty in evaluation of patients with known juvenile rheumatoid arthritis and coexistent septic arthritis, and to discuss the methods used to differentiate between the two conditions

20. SHAO LH, WEI M, DONG M: [Diagnosis and prognosis of systemic juvenile rheumatoid arthritis]. Zhonghua Er Ke Za Zhi 41:1 46-47, 2003

21. SOKKA T, WILLOUGHBY J, YAZICI Y, PINCUS T: Databases of patients with early rheumatoid arthritis in the USA. Clin Exp Rheumatol 21:5 Suppl 31 S146-S153, 2003
    Organism: Vanderbilt University Medical Center, Nashville, Tennessee, USAFAU - Sokka, T
    Abstract: Several databases of patients with early rheumatoid arthritis (RA) have been established in the USA. The University of Tennessee at Memphis Cohort was organized in 1967-1971 to enroll 50 young adults (16-44 years) with symptom onset of < or = 6 months who met the 1958 American Rheumatism Association (ARA) criteria for at least probable RA. Two important observations from this database were that many patients seen within the first 6 months of meeting the criteria for probable RA have a self-limited rather than progressive disease, and that progressive disease is predicted by a high number of baseline swollen and tender joints. The National Institutes of Health (NIH) cohort of patients with peripheral synovitis for > or = 6 weeks but < 12 months in at least one peripheral joint was established in 1994. At the one-year follow-up, 45% of the patients met the RA criteria, 9% had reactive arthritis, 6% had psoriatic arthritis, 5% had other rheumatic diseases, and 35% had undifferentiated arthritis. The number of active joints, rather than meeting the criteria for RA, was the primary determinant of function and performance after one year. The Western Consortium of Practicing Rheumatologists (CPR) was established in 1993 to enroll patients with an RA duration < 1 year, positive rheumatoid factor, > or = 6 swollen and > or = 9 tender joints, and no previous treatment with disease modifying anti-rheumatic drugs (DMARDs). Data from this cohort indicated the validity of self-report joint counts. American College of Rheumatology 20% improvement (ACR20) responses were seen in 50% of patients at 6 months and in 57% of patients at 24 months, while antinuclear antibodies (ANA) were seen in 69% of patients prior to the availability of biologic agents. The North American Cohort of Patients with Early RA (SONORA), which included patients with symptoms for > 3 but < 12 months, indicated that methotrexate (MTX) was the most frequently prescribed DMARD, being taken by more than half the patients. The Consortium for the Longitudinal Evaluation of African-Americans with RA (CLEAR) registry and DNA repository has enrolled 123 African-American patients with early RA of less than 2 years' duration to analyze genetic and non-genetic factors associated with disease severity. The Early RA Treatment Evaluation Registry (ERATER) of patients with early RA (< 3 years) was established in 2001. In this registry, MTX was the first DMARD used in 83% of patients, and most patients would not meet the criteria for inclusion in recent clinical trials of biological agents. Further observation of recent cohorts of patients with early RA over the next decade should be informative regarding whether aggressive intervention strategies and new DMARDs and biologic agents lead to improved long-term outcomes

22. STARY J, HOUSKOVA J, SPISEK R, VAVRA V, SEDLACEK P, MIHAL V, SMISEK P, HRUSAK O, ZDRAHALOVA K, SRAMKOVA L, KESLOVA P, KOMRSKA V, CINEK O, KODET R: Hemophagocytic Lymphohistiocytosis - Diagnostic and Therapeutic Dilemma
    HEMOFAGOCYTUJICI LYMFOHISTIOCYTOZA - DIAGNOSTICKE A LECEBNE DILEMA. Cesko-Slovenska Pediatrie (Czech Republic ) 59:2 70-82, 2004
    Abstract: Syndrome of hemophagocytic lymphohistiocytosis (HLH) is characterized by uncontrolled proliferation of T lymphocytes and macrophages. HLH develops in patients with primary or secondary immunodeficiency. Overproduction of cytokines plays a major role in the tissue damage and in the development of typical clinical and laboratory features - persistent fever, hepatosplenomegaly, peripheral blood cytopenia, hypertriglyceridemia, hypofibrinogenemia and bone marrow hemophagocytosis. Two forms of HLH exist: primary HLH - a heterogenous group of rare genetic disorders and a secondary form, associated with systemic infections, malignancies or systemic autoimmune diseases. HLH is a life-threatening acute illness frequently progressing into the multiorgan failure and death. Establishment of diagnosis and the appropriate choice of therapy are often difficult. Both forms of HLH respond well to the immunosuppressive therapy. Stem cell transplantation offers the only curative treatment strategy for children with the primary HLH. Diagnostic and therapeutic dilemma is demonstrated on case-reports of patients suffering from familial hemophagocytic lymhohistiocytosis, Chediak-Higashi syndrome, fatal infectious mononucleosis, visceral leishmaniasis, large cell anaplastic lymphoma, secondary malignant histiocytosis and macrophage activation syndrome associated with juvenile idiopathic arthritis. Awarness of differential diagnosis of HLH, application of modern diagnostic methods and an early initiation of the efficient treatment improve the prognosis of these unfavourable disorders

23. STEPHAN JL: Hemophagocytic syndromes and primary immunodeficiency
    <ORIGINAL> Syndromes hemophagocytaires et deficits immunitaires primitifs. Archives De Pediatrie 10:Suppl. 4 517s-520s, /9
    Abstract: Lymphohistiocytic activation syndromes are characterized by activation and proliferation of T cells and macrophages usually reflecting an inappropriate response of the host to an infection. The clinical manifestations are often alarming symptoms suggestive of severe sepsis. Most patients have a known underlying disease (hemopathy, lupus, Still's disease, HIV infection, bone marrow or organ transplantation). In the few cases that occur apparently without any risk factors, investigations should be done to look for a predisposing inherited disease such as familial lymphohistiocytosis or Purtilo syndrome in boys. The treatment relies on immunosuppressive agents followed by bone marrow transplantation, which can provide a definitive cure in genetics forms

24. SYMMONS DP, SILMAN AJ: The Norfolk Arthritis Register (NOAR). Clin Exp Rheumatol 21:5 Suppl 31 S94-S99, 2003
    Organism: Arthritis Research Campaign Epidemiology Unit, School of Epidemiology and Health Sciences, University of Manchester, Stopford Building, Oxford Road, Manchester M13 9PT, United Kingdom DeborahSymmons@manacukFAU - Symmons, D P
    Abstract: The Norfolk Arthritis Register (NOAR) has been recruiting and following patients with early inflammatory polyarthritis (IP) since 1989. Approximately three-quarters of the patients followed satisfy classification criteria for rheumatoid arthritis (RA) by 5 years from symptom onset. This paper summarises the publications which have been based on the NOAR cohort with respect to the incidence and prevalence of IP and RA, genetic and environmental risk factors for the development of IP, outcome following the development of IP and predictors of outcome. It also discusses methodological issues in examining the treatment effect in observational cohorts and the costs to the healthcare system of patients with early IP

25. ZEIDLER H, MERKESDAL S, HULSEMANN JL: Early arthritis and rheumatoid arthritis in Germany. Clin Exp Rheumatol 21:5 Suppl 31 S106-S112, 2003
    Organism: Division of Rheumatology, Department of Internal Medicine, Medical School Hannover, Carl-Neuberg-Str 1, 30625 Hannover, Germany zeidlerhenning@mh-hannoverdeFAU - Zeidler, H
    Abstract: Early arthritis is challenging because the clinical picture often does not allow a distinction between rheumatoid arthritis (RA), self-limiting disease, and other forms of inflammatory arthritis. In Germany the first early synovitis clinic and several inception cohorts of patients with early RA were initiated and evaluated during the 1980s and 1990s to learn more about diagnostic classification, psycho-social problems and socio-economical status including sick-leave, work loss, and indirect costs of patients with early arthritis and early RA. Unclassified arthritis was described as the most frequent diagnosis and the term "undifferentiated arthritis" was chosen to underline the heterogeneity of theses arthritides and the preliminary state of this classification as a working diagnosis. A large National Databank of the German Regional Collaborative Arthritis Centres has been established over the last 10 years. In total, there are some 170,000 cases in the database. Moreover, a prospective multicentre inception cohort of early RA of less than 1 year's disease duration has been started recently to evaluate parameters of potential relevance for the pathogenesis of RA and eventually for the prediction of erosive disease. Studies are in progress to test the diagnostic performance of specific antibodies and antibody patterns for RA. Another topic of research addresses the identification of bacterial DNA in synovial fluid and synovial tissues to improve the differentiation of patients with reactive arthritis from those with early RA and to narrow the working diagnosis of undifferentiated arthritis