Bibliography September 2003

1. ANDRES E, IMLER M: A patient with adult Still's disease and high Chlamydia trachomatis titers. Journal of Infection and Chemotherapy 9:2 194, 2003

2. BAKSIENE D, KASPARAVICIENE J, ZEBIENE M, PUTELIENE B: [Juvenile idiopathic systemic arthritis]. Medicina (Kaunas) 39:8 751-755, 2003
   Organism: Clinics of Pediatrics, Kaunas University of Medicine, 3007 Kaunas, Lithuania childdgn@kmultFAU - Baksiene, Dalia
   Abstract: THE PURPOSE OF THE STUDY was to evaluate the peculiarities of the clinical features, laboratory parameters and tactics of treatment in juvenile idiopatic systematic arthritis. METHODS: A retrospective data review of 41 children (26 boys and 15 girls) who underwent treatment for systemic arthritis (according to ILAR criteria) in our institution between 1992 and 2002 was performed. RESULTS: The disease started with fever of unknown origin in all cases. In 73% of patients it lasted longer than one month, in 54% fever was with twice daily spikers in the morning and in the evening. The rash during the rise of temperature appeared in 49%, in most cases (70%) there was a maculo-papular rash. Lymphadenopathy and serositis were observed in 32%, hepatomegaly in 29%, and splenomegaly in 24%. Arthritis coincided with the fever in 29% of patients, in majority of cases it was progressing to a severe persistent arthritis after the systematic phase. There was no specific laboratory findings: neutrophilic leucocytosis was found in 73%, anemia - in 80.5%, trombocytosis - in 36.6%, elevated CRP - in 63.4%, dysproteinemia - in 79% of patients. Antinuclear factors were absent in all examined children. For all patients intravenous methylprednisolone pulses have been administered (10-22 mg/kg/infusion). Prednisolone was also continued orally (1-2 mg/kg/day). 24.4% of patients required in addition immunosupressive agents such as methotrexate, azathioprine and cyclophosphamide. CONCLUSION: Puls-therapy of methylprednisolone is a safe and sufficiently effective method of treatment in most cases of the systematic juvenile arthritis

3. BENDTZEN K, HANSEN PR, RIENECK K: Spironolactone inhibits production of proinflammatory cytokines, including tumour necrosis factor-alpha and interferon-gamma, and has potential in the treatment of arthritis. Clin Exp Immunol 134:1 151-158, 2003
   Organism: Rigshospitalet National University Hospital, Copenhagen, Denmark kben@maildkFAU - Bendtzen, K
   Abstract: Evidence suggests that spironolactone, an aldosterone antagonist, has effects on many cell types independent of its binding to cytosolic mineralocorticoid receptors. We tested the effects of spironolactone on ex vivo-activated human blood leucocytes using gene expression analyses (GeneChip, 12,000 genes) and enzyme immunoassay for quantitating secreted pro- and anti-inflammatory cytokines. Furthermore, to evaluate the safety and efficacy of spironolactone as an anti-inflammatory drug 21 patients with rheumatoid arthritis (RA), juvenile idiopathic arthritis (JIA) or other arthritides were treated for up to 22 months with 1-3 mg/kg/day. Spironolactone, at in vivo attainable doses, markedly suppressed transcription of several proinflammatory cytokines and, accordingly, inhibited release of tumour necrosis factor, lymphotoxin, interferon-gamma, granulocyte-macrophage colony-stimulating factor and interleukin 6 (70-90% inhibition). Release of these cytokines was also suppressed when testing whole blood from RA patients receiving 50 mg spironolactone twice daily, indicating that pharmaceutical use of the drug may suppress the release of inflammatory cytokines. Spironolactone therapy was generally well tolerated, although treatment had to be stopped in two adults on concomitant methotrexate therapy. Sixteen patients (76%) responded favourably. American College of Rheumatology criteria (ACR)20 or better was achieved in six of nine RA patients; four reached ACR70. Eight of nine JIA patients improved. In conclusion, spironolactone inhibits production of several proinflammatory cytokines considered to be of pathogenic importance in many immunoinflammatory diseases and shows positive effect in patients with chronic arthritis. Its effect as an anti-inflammatory drug should be explored, because prolonged spironolactone therapy is reasonably safe and economically attractive compared with many modern anti-inflammatory therapies

4. BRASIL TB, FERRIANI VP, MACHADO CS: [Health related quality of life survey about children and adolescents with juvenile idiopathic arthritis]. J Pediatr (Rio J) 79:1 63-68, 2003
   Organism: Faculdade de Medicina de Botucatu, UNESP, Botucatu, SP, BrazilFAU - Brasil, Tatiana B
   Abstract: OBJECTIVE: To study the impact of chronic arthritis on health related quality of life by means of two self-reported tools: the parents' version of the Childhood Health Assessment Questionnaire (CHAQ) and the Childhood Health Questionnaire PF50\'ae (CHQ).\par METHODS: Both tools were filled in after proper instructions by 36 parents, during 1-2 clinic visits. The Disability Index (CHAQ) and the Physical and Psychosocial scores (CHQ) were compared to the core set of outcome measures, namely 1) physician's global assessment, 2) parents' global assessment, both scored by 10 cm visual analogue scale, 3) number of joints with active arthritis, 4) number of joints with limited range of motion, 5) erythrocyte sedimentation rate.\par RESULTS: There was significant difference for all measures of disease activity, being higher in the polyarticular as compared to oligoarticular except for erythrocyte sedimentation rate, parents' global assessment, and psychosocial score. This leads to different parents' perceptions of disease activity and outcome. The responsiveness of the outcome measures during two follow-up visits of patients receiving active treatment indicated better responsiveness of physicians' global assessment among the subjective measures, and intermediate responsiveness of the self-reported measures in comparison to the number of active and limited joints, and erythrocyte sedimentation rate. \par CONCLUSIONS: The responsiveness of two health related quality of life tools indicates their relative sensitivity for assessing clinical improvement during active treatment in Juvenile Idiopathic Arthritis patients.\par

5. CHOUNG Y, PARK K, MOON S, KIM C, RYU S: Various causes and clinical characteristics in vertigo in children with normal eardrums. International Journal of Pediatric Otorhinolaryngology 67:8 889-894, 2003
   Abstract: Objective: The differential diagnosis of vertigo in children is extensive. Otitis media and middle ear effusion could be the most common causes of vertigo in children, but there are some problems in detecting the other causes for vertigo because they are one of most frequent diseases of childhood. The purpose of this study is to review the clinical characteristics and both the audiological and vestibular findings of vertigo in children with normal eardrums, who do not show otitis media or middle ear effusion, and to assist in making a differential diagnosis of vertigo. Methods: The fifty five children (<16 years old) with vertigo, who visited the Department of Otolaryngology, Ajou University Hospital, Suwon, South Korea between January 1995 and December 2001 were selected for this study. These excluded the patients with abnormal eardrums/tympanograms or those that did not perform questionnaires, audiological, or vestibular evaluations. They were retrospectively analyzed for clinical symptoms, vestibular functions, and differential diagnosis. Results: The most common causes for vertigo in children were migraine in 17 (30.9%) and benign paroxysmal vertigo of childhood (BPVC) in 14 (25.5%). Other less frequent causes included four cases of trauma, two cases each of Meniere's disease, delayed endolymphatic hydrops, benign positional vertigo, and one case only for cerebellopontine angle tumor, seizure, acute vestibular neuritis, juvenile rheumatoid arthritis, leaving ten cases (18.2%) as unclassified. Abnormal findings were noted in 13 (23.6%) in pure tone audiogram, 3 (5.5%) in positioning test, 6 (10.9%) in bithermal caloric test, and 36 (65.5%) in rotation chair test. Conclusions: The vertigo in children with normal eardrums, who did not show otitis media or middle ear effusion, was most commonly caused by migraine and BPVC. These findings have shown to be very different from those with adult vertigo. The evaluation of vertigo in children requires a questionnaire for extensive and complete history taking, audiograms and vestibular function tests. And in selected cases, electroencephalography, hematological evaluation, imaging of the brain or temporal bone should be performed

6. DOUGLAS M, BRADBURY R, KANNANGARA S, MITCHELL D: Arthritis as an unusual manifestation of Kikuchi-Fujimoto disease. Rheumatology (Oxford) 42:8 1010-1012, 2003

7. FROSCH M, VOGL T, SEELIGER S, WULFFRAAT N, KUIS W, VIEMANN D, FOELL D, SORG C, SUNDERKOTTER C, ROTH J: Expression of myeloid-related proteins 8 and 14 in systemic-onset juvenile rheumatoid arthritis. Arthritis Rheum 48:9 2622-2626, 2003
   Organism: Institute of Experimental Dermatology and Department of Pediatrics, University of Munster, Munster, GermanyFAU - Frosch, Michael
   Abstract: OBJECTIVE: To analyze which cellular compartments are involved in the initial phase of systemic-onset juvenile rheumatoid arthritis (JRA), and to investigate the role that myeloid-related protein 8 (MRP-8) and MRP-14, two S-100 proteins that are primarily expressed in phagocytes, play in the disease. METHODS: Skin biopsy samples obtained during patients' acute episodes of systemic-onset JRA were analyzed by immunohistochemistry and in situ hybridization. Concentrations of MRP-8/MRP-14 in serum were determined by enzyme-linked immunosorbent assay. RESULTS: By analyzing biopsy samples from cutaneous rashes during the initial phase of systemic-onset JRA, we discovered infiltration of leukocytes expressing MRP-8 and MRP-14. Surprisingly, keratinocytes also showed de novo synthesis of these proinflammatory proteins, indicating activation of epithelial cells during systemic-onset JRA. Serum concentrations of MRP-8/MRP-14 were 120-fold higher compared with healthy controls and approximately 12-fold higher compared with patients with other inflammatory diseases. Concentrations of MRP-8/MRP-14 in patients with systemic-onset JRA fell dramatically after remission was induced. CONCLUSION: The exceptionally high serum levels of MRP-8 and MRP-14 in active systemic-onset JRA make them prime candidates as markers for monitoring disease activity and response to treatment. Since MRP-8/MRP-14 exhibit direct effects on leukocyte adhesion to the vascular endothelium, their extensive expression in the epidermis indicates an active role for these S-100 proteins in the initial phase of this systemic autoimmune disease

8. GARE BA, FASTH A: The outcome of juvenile idiopathic arthritis. Current Paediatrics (United Kingdom ) 13:5 327-334, 2003
   Abstract: To evaluate outcome studies for childhood arthritides, we need to consider the heterogeneity of the disease, the criteria used to define the condition and how the population investigated was chosen. In this review, population- and hospital-based studies from the last 10 years were analysed. Due to the heterogeneity, continuing disease activity varied between 39 and 67% for all subgroups with the best prognosis for persistent oligoarthritis. Disability measured by CHAQ/HAQ showed that at least one-third of patients report some impact of the disease, but severe disability was rare. Many studies also report lower quality of life in patients compared with controls. Risk factors for disability were female sex, a polyarticular disease course and positive IgM rheumatoid factor. In summary, juvenile idiopathic arthritis is both a self-limiting disease and a progressive disease, which creates disability and decreased quality of life. There seem to be differences in the quality of life and participation in society between nations, and further studies from different parts of the world are necessary. This research should include the perspective of patients and their families. (c) 2003 Elsevier Ltd. All rights reserved

9. GROM AA: Macrophage activation syndrome and reactive hemophagocytic lymphohistiocytosis: the same entities? Curr Opin Rheumatol 15:5 587-590, 2003
   Organism: Cincinnati Children's Hospital Medical Center, OH 45215, USA groma0@cchmcorgFAU - Grom, Alexei A
   Abstract: PURPOSE OF THE REVIEW: One of the most perplexing features of systemic-onset juvenile rheumatoid arthritis is the association with macrophage activation syndrome, a life-threatening complication caused by excessive activation and proliferation of T cells and macrophages. The main purpose of the review is to summarize current understanding of the relation between macrophage activation syndrome and other clinically similar hemophagocytic disorders. RECENT FINDINGS: Clinically, macrophage activation syndrome has strong similarities with familial and virus-associated reactive hemophagocytic lymphohistiocytosis. The better understood familial hemophagocytic lymphohistiocytosis is a constellation of rare, autosomal recessive immune disorders. The most consistent immunologic abnormalities in patients with familial hemophagocytic lymphohistiocytosis are decreased natural killer and cytotoxic cell functions. In approximately one third of familial hemophagocytic lymphohistiocytosis patients, these immunologic abnormalities are secondary to mutations in the gene encoding perforin, a protein that mediates cytotoxic activity of natural killer and cytotoxic CD8+ T cells. Several recent studies have suggested that profoundly depressed natural killer cell activity and abnormal levels of perforin expression may be a feature of macrophage activation syndrome in systemic-onset juvenile rheumatoid arthritis as well. Although it has been proposed that in both hemophagocytic lymphohistiocytosis and macrophage activation syndrome, natural killer and cytotoxic cell dysfunction may lead to inadequate control of cellular immune responses, the exact nature of such dysregulation and the relation between macrophage activation syndrome and hemophagocytic lymphohistiocytosis still remain to be determined

10. HELLER A, RUBTSOV N, TRIFONOV V, STARKE H, LONCAREVIC I, CLAUSSEN U, LIEHR T: Characterization of complex aberrant leukemia cases by means of multicolor banding (MCB). European Journal of Human Genetics 9:Supplement 1 0171,

11. JEDRZEJCZYK-GORAL B, PRUSEK W, OWCZAREK H, NAHACZEWSKA W: Markers of bone turnover in children with juvenile chronic arthritis - Part II
    MARKERY METABOLIZMU KOSTNEGO U DZIECI Z Ml(stroke)ODZIENCZYM PRZEWLEKl(stroke)YM ZAPALENIEM STAWOW - CZESC II. Advances in Clinical and Experimental Medicine (Poland ) 12:4 449-459, 2003
    Abstract: Objectives. We wanted to estimate, if the therapy of juvenile chronic arthritis (steroids, non-steroid antiinflammatory therapy and others) has influence on bone turnover and how markers of bone turnover behave in others connective tissue diseases? Material and Methods. 29 healthy children and 52 children with juvenile chronic arthritis, 11 with lupus erythematosus, 3 with dermatomyositis, 3 with osteoporosis, 2 with Schonlein-Henoch disease, 1 with poliartheritis nodosa and 1 with sclerodermic were studied. All children were 3-18 age. In study of bone turnover we used: markers of bone formation - PICP, T-ALP, B-ALP and markers of bone resorption - ICTP, DPD. Results. Children with steroid therapy and children with non-steroid antiinflammatory therapy had significantly deceased PICP, T-ALP and B-ALP. The younger children in age 3-11 had high significantly low PICP, T-ALP, B-ALP and significantly low ICTP. Children with diagnosis lupus erythematosus had only significantly low ICTP. Conclusions. Because of unfavourable influence on bone turnover, there is very important reasonably planning of steroid and non-steroid antyinflammatory therapy in children specially in younger children

12. KAKAR S, NEHRA V, MURRAY JA, DAYHARSH GA, BURGART LJ: Significance of intraepithelial lymphocytosis in small bowel biopsy samples with normal mucosal architecture. Am J Gastroenterol 98:9 2027-2033, 2003
    Organism: Department of Pathology, Mayo Clinic, Rochester, Minnesota 55905, USAFAU - Kakar, Sanjay
    Abstract: OBJECTIVES: The aim of this study was to determine the specificity of increase in intraepithelial lymphocytes (IELs) with normal villous architecture in small bowel biopsy samples for diagnosis of gluten sensitivity (GS) and its significance in the absence of GS. METHODS: Small bowel biopsy samples from 43 patients with increased IELs and no other pathology were reviewed. Patients with prior diagnosis of GS were excluded. A group of 46 patients with normal duodenal biopsy during the same period served as controls. The clinical records of patients and controls were examined for presenting symptoms, laboratory tests, and final clinicopathological diagnosis. Immunohistochemical characterization of IELs was performed in 13 cases. RESULTS: Four (9.3%) patients had GS based on positive IgA antiendomysial antibodies (n = 3) and favorable response to gluten-free diet (n = 4). One patient (2.2%) had partially treated tropical sprue; six patients (14%) had disorders of immune regulation including Hashimoto's thyroiditis (n = 2) and one case each of Graves' disease, rheumatoid arthritis, psoriasis, and multiple sclerosis; and six patients (14%) were on nonsteroidal anti-inflammatory drugs (NSAIDs). In contrast, none of the control subjects had GS (p = 0.05), tropical sprue, or immunoregulatory disorders (p = 0.011), and one (2.2%) was on NSAIDs (p = 0.04). Increased IELs were also observed in Crohn's disease, lymphocytic/collagenous colitis, and bacterial overgrowth, but the association did not reach statistical significance. Histological features (number and distribution of IELs, crypt mitoses) and immunophenotypic analysis of IELs did not reliably distinguish GS-related from non-GS-related causes of increased IELs. CONCLUSIONS: Intraepithelial lymphocytosis in an otherwise normal small bowel biopsy is somewhat nonspecific, but in nearly 10% of cases can be the initial presentation of GS. Therefore all patients with this finding should be investigated for GS. Increased IELs may also be associated with autoimmune disorders and NSAIDs

13. KEKILLI E, YAGMUR C, AYDIN OM: Cervical involvement in juvenile-onset ankylosing spondylitis with bone scintigraphy. Rheumatol Int .: 2003
    Organism: Department of Nuclear Medicine, Inonu University, Turgut Ozal Medical Center, Elazig Avenue, 7 km, Malatya, Turkey
    Abstract: Juvenile-onset ankylosing spondylitis is an unusual disorder which can present with either peripheral arthritis or more classic hip girdle and back symptoms. A 12-year-old child with this disease was admitted with walking disorder, cervical pain, restricted cervical motion, and right ankle swelling. Diffusely increased accumulation of radioactivity in the cervical spine, focally increased accumulation in bilateral sacroiliac joints, and diminished irregular uptake in thoracal spine were detected on technetium 99m methylene diphosphonate bone scintigraphy. As a result, this imaging technique may give important information for diagnosis and differential diagnosis in juvenile chronic arthritis

14. KISS S, LETKO E, QAMRUDDIN S, BALTATZIS S, FOSTER CS: Long-term progression, prognosis, and treatment of patients with recurrent ocular manifestations of Reiter's syndrome. Ophthalmology 110:9 1764-1769, 2003
    Organism: Department of Ophthalmology, The Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts 02114, USAFAU - Kiss, Szilard
    Abstract: PURPOSE: To investigate the spectrum of ocular involvement, to examine the clinical outcome, and to analyze the influence of treatment in patients with chronic ocular manifestations of Reiter's syndrome (RS) referred to a tertiary care ocular immunology service. DESIGN: Retrospective, noncomparative, interventional case series. PARTICIPANTS: Twenty-five patients with RS evaluated at the Ocular Immunology and Uveitis Service of the Massachusetts Eye and Ear Infirmary from 1981 through 2001. METHODS: Charts of patients were reviewed and data on age, gender, follow-up time, ocular symptoms, extraocular involvement, ocular complications, therapy, and visual acuities were recorded. MAIN OUTCOME MEASURES: Visual acuity, ocular complications, disease progression, clinical outcome, and systemic treatment. RESULTS: Twenty-five patients (20 male and 5 female) diagnosed with RS, with a mean age at presentation to our service of 37 years, were studied. The mean follow-up was 48.5 months. Eighty-five percent of patients tested were positive for human leukocyte antigen B27. Sixty-four percent of patients had a positive family history. All patients had oligoarthritis and enthesitis, most commonly affecting the back (56%), Achilles tendon (52%), and sacroiliac joint (24%). Eighty percent had a history of infection, most frequently urethritis (68%). Forty-four percent had a history of mucocutaneous lesions. All patients demonstrated ocular involvement at the time of diagnosis (68% with unilateral and 32% with bilateral disease), 84% had evidence of uveitis, 3% had scleritis, 2% had conjunctivitis, and 1% had pars planitis and iridocyclitis. During follow-up, the ocular complications included conjunctivitis (96%), anterior uveitis (92%), posterior uveitis (64%), keratitis (64%), cataract (56%), intermediate uveitis (40%), scleritis (28%), cystoid macular edema (28%), papillitis (16%), and glaucoma (16%). Systemic treatment for ocular inflammation was initiated in all patients. Ninety-six percent were treated with nonsteroidal anti-inflammatory agents. Eighty-eight percent were treated with corticosteroids, 64% requiring systemic prednisone. Immunosuppressive therapy was initiated in 52% of patients, with all receiving methotrexate. Seven patients required more than one immunosuppressive agent. The mean initial visual acuity was 20/25 in the right eye and 20/30 in the left eye. The mean final visual acuity was 20/25 in the right eye and 20/25 in the left eye. CONCLUSIONS: Reiter's syndrome may be associated with chronic recurrent ocular inflammation. Systemic therapy (including immunosuppressive treatment) typically is required to control the ocular inflammation and to prevent progressive visual loss

15. KORCZOWSKI B, KOWALCZYK JR, BIJAK M, RUSIN J: Concentration of procalcitonin and C-reactive protein in serum and erythrocyte sedimentation rate in active autoimmune diseases in children
    PROKALCYTONINA, BIAl(stroke)KO C-REAKTYWNE I ODCZYN OPADANIA KRWINEK CZERWONYCH W AKTYWNEJ FAZIE CHOROB AUTOIMMUNIZACYJNYCH U DZIECI. Polski Merkuriusz Lekarski (Poland ) 15:86 155-157, 2003
    Abstract: Procalcitonin (PCT), a 116 amino acid prohormon of calcitonin is a new acute phase reactant with features different to other markers of inflammatory response. The aim of the study was to compare PCT and C-reactive protein (CRP) levels and erythrocyte sedimentation rate (ESR) in active autoimmune diseases in children. PCT, CRP and ESR were determined in 28 children with active autoimmune process in course of various diseases: ulcerative colitis (n=7), Lesniowski-Crohn disease (n=2), juvenile chronic arthritis (n=9), autoimmune haemolytic anaemia (n=4), dermatomyositis (n=2), sklerodermia (n=1), systemic lupus erythematodes (n=1), Behcet's syndrome (n=1), primary sclerosing cholangitis (n=1). Serum PCT levels were measured by immunoluminometric assay, CRP by turbidometric assay, ESR was counted in millimetres after one hour. PCT exceeded 0.5 ng/ml in 5 cases (range: 0.0-2.4 ng/ml; mean: 0.4+0.1 ng/ml); CRP was above 0.5 mg/dl in 24 children (range: 0.2-25.9 mg/dl; mean: 7.1+/-1.2 mg/dl); ESR was above 10 mm/h in all but 2 cases (range: 3-124 mm/h; mean: 57+/-7 mm/h). Conclusion: contrary to CRP and ESR, serum PCT level in children with autoimmune diseases remains low. However in some children with highly active autoimmune process slight elevation of PCT concentration is observed without evidence of bacterial infection

16. KOTANIEMI K, SAVOLAINEN A, KARMA A, AHO K: Recent advances in uveitis of juvenile idiopathic arthritis. Surv Ophthalmol 48:5 489-502, 2003
    Organism: Rheumatism Foundation Hospital, Heinola, FinlandFAU - Kotaniemi, Kaisu
    Abstract: Chronic scarring-type uveitis is a frequent extra-articular manifestation of juvenile idiopathic arthritis. It occurs in about 20% of children with this disease, commencing typically within a few years from its onset. The risk of uveitis is greatest in antinuclear antibody-positive girls with early onset oligoarthritis. The classic clinical picture is chronic bilateral anterior uveitis, usually asymptomatic until substantial damage to intraocular structures occurs. In view of the asymptomatic nature of the condition, routine screening of juvenile idiopathic arthritis patients 2-4 times a year is crucial to prevent complications. The treatment consists of topical corticosteroids and mydriatics, in severe cases with immunosuppressive agents, and surgical management of complications. Although the prognosis of uveitis is improving, there are cases refractory to standard regimens. Patients in whom uveitis commences prior to the onset of arthritis present a special problem

17. LANGER H-E, EHLEBRACHT-KONIG I, MATTUSSEK S: Quality assurance of rheumatologic patient education
    QUALITATSSICHERUNG BEI DER RHEUMATOLOGISCHEN PATIENTENSCHULUNG. Zeitschrift fur Arztliche Fortbildung und Qualitatssicherung (Germany ) 97:6 357-363, 2003
    Abstract: Since 1989 patient education programmes for patients with rheumatoid arthritis, ankylosing spondylitis and other spondylarthropathies, systemic lupus erythematosus, vasculitis, fibromyalgia, and juvenile chronic arthritis and their parents have been developed by an interdisciplinary team of the German Society of Rheumatology (Deutsche Gesellschaft fur Rheumatologie). Up to date, about 500 people were trained to be group leaders or specialised trainers with an associated train-the-trainer program. In 1999, the Society discharged preliminary guidelines for patient education in rheumatology. Prospective randomised studies demonstrated that patient education led both to an improvement of knowledge self-efficacy and self-help activities and to an improvement of arthritis-related helplessness and pain, and a reduction of both temporary and permanent disability

18. LO RI, V, FISHMAN NO, NACHAMKIN I: Recurrent catheter-related Rhodotorula rubra infection. Clinical Microbiology and Infection (United Kingdom ) 9:8 897-900, 2003
    Abstract: A 34-year-old male receiving chronic parenteral nutrition for treatment of short bowel syndrome and intermittent immunosuppressive agents for juvenile rheumatoid arthritis developed recurrent, catheter-associated Rhodotorula rubra fungemia over a one-year period. Infection with this yeast is associated with insertion of central venous catheters. Recurrence of R. rubra infection is an unusual event that presumably occurred because of chronic skin colonization by the organism

19. MARTINI A: Are the number of joints involved or the presence of psoriasis still useful tools to identify homogeneous disease entities in juvenile idiopathic arthritis? J Rheumatol 30:9 1900-1903, 2003

20. MASI L, BECHERINI L, PISCITELLI E, BENVENUTI S, SIMONINI G, FALCINI F, FALCHETTI A, TANINI A, IMBRIACO R, BRANDI M: Osteoprotegerin (OPG) serum levels and OPG polymorphism in children with polyarticular juvenile idiopathic arthritis. J Bone Miner Res 17:Suppl 1 S324, 2002

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

22. MONTEIRO DE CASTRO TC, TERRERI MT, LEN C, ESTEVES HILARIO MO: Treatment of refractory juvenile idiopathic arthritis via pulse therapy using methylprednisolone and cyclophosphamide. Sao Paulo Medical Journal (Brazil ) 121:3 117-120, 2003
    Abstract: Context: Patients with refractory juvenile idiopathic arthritis can benefit from aggressive therapy. Case Report: We followed the clinical course of 4 patients (2 male, 2 female) aged 9.1-17.8 years (mean of 14.5 years) with polyarticular onset of juvenile rheumatoid arthritis and one 16-year-old boy with juvenile spondyloarthropathy associated with inflammatory bowel disease. All the juvenile rheumatoid arthritis patients fulfilled the diagnostic criteria established by the American College of Rheumatology. All patients had unremitting arthritis despite maximum therapy. All patients began receiving treatment using intravenous cyclophosphamide at 500-750 mg/mSUP2 and intravenous methylprednisolone at 30 mg/kg, for 3 days monthly (1 g maximum). The patients received between 3 and 11 monthly treatments, and/or 3-5 treatments every two months for 12 months, according to the severity of the disease and/or response to the therapy. All but one patient were evaluated retrospectively at the start (time 0) and 6 months (time 1), and 12 months (time 2) after the beginning of the treatment. A rapid and clinically significant suppression of systemic and articular manifestations was seen in all patients. Our results showed the favorable effect of this treatment on the clinical and some laboratory manifestations of juvenile idiopathic arthritis

23. MRSIC M, STAVLJENIC-RUKAVINA A, FUMIC K, LABAR B, BOGDANIC V, POTOCKI K, KARDUM-SKELIN I, ROVERS D: Management of Gaucher disease in a post-communist transitional health care system: Croatian experience. Croat Med J 44:5 606-609, 2003
    Organism: Division of Hematology, Department of Internal Medicine, Zagreb University Hospital Center, Kispaticeva 12, 10000 Zagreb, Croatia mirandomrsic@inethrFAU - Mrsic, Mirando
    Abstract: AIM: To evaluate the feasibility of financing the treatment of Gaucher disease with recombinant human imiglucerase in the Croatian health care system. METHODS:Treatment with enzyme replacement therapy of 5 patients with Gaucher disease was started on January 2001. In 4 patients the typical signs of Gaucher disease (organomegaly, bone changes, anemia, and thrombocytopenia) were documented at the time of diagnosis. One patient received bone marrow stem cell transplant as treatment for acute myeloid leukemia from a HLA-matching sibling with Gaucher disease. All patients underwent therapy with imiglucerase (Cerezyme) infusion every 14 days. The outcome and actual cost of the treatment were followed during 12 months. RESULTS: After 3 months of therapy, hemoglobin rose above low normal range in 2 patients. After 6 months, 3 patients had platelet count above 100x10(9)/L, and bone pain crises completely disappeared in patients with severe bone involvement. After 12 months, normal blood counts were restored in all patients. At the same time point, bone destruction remained unchanged in 3 patients and showed marked improvement in one. In agreement with the Ministry of Health, the Croatian Institute for Health Insurance restructured its funds and established a special "Fund for expensive drugs." This fund covers the treatment costs for patients with Gaucher disease (approximately 150,000 per patient per year) as well as the cost of treatment for patients with Fabry disease, AIDS, adenosine deaminase deficiency, multiple sclerosis, chronic myeloid leukemia, juvenile arthritis, and ovarian cancer. CONCLUSION: Collaboration of the institutions in a post-communist transition health care system can provide an effective model for financing expensive treatment for patients with rare diseases in a resource-poor health system

24. NEBEN MA, MORICE WG, TEFFERI A: Clinical features in T-cell vs. natural killer-cell variants of large granular lymphocyte leukemia. Eur J Haematol 71:4 263-265, 2003
    Organism: Division of Hematology and Internal Medicine; Division of Hematopathology, Mayo Clinic, Mayo Medical School, Rochester, MN 55905, USAFAU - Neben, Michelle A
    Abstract: OBJECTIVE: Standard clinical and laboratory evaluations and novel laboratory techniques were used to identify patients with T-cell large granular lymphocyte leukemia (LGLL) and those with natural killer-cell variants of LGLL for comprehensive clinical evaluation. METHODS: We used bone marrow histologic analysis, immunophenotypic markers of clonality, and T-cell-receptor gene rearrangement studies to identify patients. RESULTS: The study identified 44 patients with T-cell LGLL and 14 with natural killer-cell LGLL. The two disorders were similar in sex and age distribution of patients; peripheral blood lymphocyte, neutrophil, and platelet counts; and incidence of rheumatoid arthritis. Among the two groups, patients with the T-cell LGLL presented with significantly lower hemoglobin concentrations (P < 0.04) and a higher frequency of palpable splenomegaly (P < 0.01). CONCLUSION: Overall disease progression and response to immunosuppressive therapy are similar between T-cell and natural killer-cell variants of LGLL

25. NIEHUES T, HORNEFF G, MICHELS H, SAILER-HOCK M, SCHUCHMANN L: Evidence-based treatment with methotrexate in children with rheumatic disorders. Consensus statement of the Working Group for Children and Adolescents with Rheumatic Diseases in Germany and the Working Group on Pediatric Rheumatology in Austria
    EVIDENZBASIERTER EINSATZ VON METHOTREXAT BEI KINDERN MIT RHEUMATISCHEN ERKRANKUNGEN. KONSENSUSSTATEMENT DER ARBEITSGEMEINSCHAFT KIND. Monatsschrift fur Kinderheilkunde (Germany ) 151:8 881-890, 2003
    Abstract: Juvenile idiopathic arthritis (JIA) is the most common diagnosis in children and adolescents with rheumatic disorders. JIA is successfully treated with nonsteroidal anti-inflammatory drugs (NSAR) and physiotherapy. Still, in a significant number of cases the disease is resistant to this therapy and treatment with "second line" disease-modifying antirheumatic drugs (DMARDs) is required. Methotrexate (MTX) is frequently referred to as a "first-choice second-line agent" for the treatment of JIA. However, in Germany MTX is not licensed for use in pediatric rheumatic diseases. To increase drug safety, the Working Group for Children and Adolescents with Rheumatic Diseases in Germany (AGKJR) and the Working Group on Pediatric Rheumatology in Austria have initiated the formulation of evidence-based recommendations. Based on consensus expert meetings, a MEDLINE search, standard textbooks and review articles, data from the central registry of the German Research Center for Rheumatic Diseases, experience with MTX in adults with rheumatoid arthritis (RA), and recommendations of the German Society of Rheumatology (DGRh), evidence and recommendations are graded and recommendations for the use of MTX in children and adolescents with rheumatic disease are presented

26. OZEN S, BAKKALOGLU A, YILMAZ E, DUZOVA A, BALCI B, TOPALOGLU R, BESBAS N: Mutations in the gene for familial Mediterranean fever: do they predispose to inflammation? J Rheumatol 30:9 2014-2018, 2003
    Organism: Department of Pediatrics, Hacettepe University, 06100 Ankara, Turkey sezaozen@hacettepeedutrFAU - Ozen, Seza
    Abstract: OBJECTIVE: To analyze 70 individuals who were found to have the Mediterranean fever (MEFV) gene for the presence of definite familial Mediterranean fever (FMF) and to assess if they were prone to clinical and laboratory inflammation. We also prospectively evaluated 72 patients with childhood rheumatic diseases for the presence of MEFV mutations. METHODS: Seventy patients with one MEFV gene mutation were reevaluated for the presence of a clinical FMF phenotype using a new set of criteria. They were also questioned for the presence of musculoskeletal symptoms and rheumatic diseases. They were sampled for erythrocyte sedimentation rates and C-reactive protein levels. A second group with childhood rheumatic diseases were diagnosed according to international criteria. RESULTS: Median age of the 70 heterozygous individuals was 12 years. About 1/3 (34.3%) were classified with clinical FMF phenotype according to the suggested criteria. Fifteen (21.4%) were classified as normal and 3 (4.3%) had recurrent abdominal pains but did not fulfill all criteria for clinical FMF. Overall, 28 (40.0%) had some form of rheumatic complaint and 15 (21.4%) had developed a rheumatic disease including Behcet's disease, a vasculitis, or acute rheumatic fever. The mean ESR and CRP levels were 45.47 +/- 33.05 mm/h and 4.00 +/- 6.73 mg/dl, respectively. Among the 72 patients with rheumatic diseases of childhood, 22 (30.5%) carried one or 2 mutations of the MEFV gene. The mutated allele frequency among patients with rheumatic diseases was significantly higher than those in controls (p < 0.05). Within this group, among the 59 patients with juvenile idiopathic arthritis 15 had mutations in the heterozygous or homozygous form. CONCLUSION: We confirm the acute phase response in the carriers for MEFV mutations. We suggest that these patients may have a tendency to develop certain manifestations due to an increased baseline of inflammation, and the presence of these mutations may affect their disease course when they develop rheumatic disease

27. ROBINSON RF, NAHATA MC, HAYES JR, RENNEBOHM R, HIGGINS G: Quality-of-life measurements in juvenile rheumatoid arthritis patients treated with etanercept. Clinical Drug Investigation (New Zealand ) 23:8 511-518, 2003
    Abstract: Objective: The aims of this study were: (1) to assess functional status, emotional well-being and quality of life in patients with polyarticular and systemic juvenile rheumatoid arthritis (JRA) treated with etanercept, and (2) to determine the prevalence and significance of adverse events associated with etanercept therapy. Patients and methods: All JRA patients (n = 21) who received etanercept in our rheumatology clinic over a 14-month period were evaluated. Patient demographics, type of arthritis, dosing regimens, family history, measures of joint function and laboratory parameters were obtained for each patient. A questionnaire that comprised validated functional assessment and quality-of-life measures (the Childhood Health Assessment Questionnaire [CHAQ(TM)], the Juvenile Arthritis Function Assessment Report [JAFAR 5(TM)] and the Pediatric Quality of Life Inventory Version 4 [PedsQL Generic Scale(TM)] scales) was administered to patients and parents to assess physical and emotional function, pain, adverse drug events and quality of life at each clinic visit. Results: Functional status and quality of life improved in patients with polyarticular and systemic disease. A significant difference between pre- and post-etanercept functional assessment (JAFAR(TM) and CHAQ(TM)) and quality-of-life assessment by parents and patients was found (p = 0.009, p = 0.002, p <= 0.001, p <= 0.001, respectively). The JAFAR(TM) results concurred with those of the CHAQ(TM) test, and did not distinguish between patients with polyarticular and systemic disease. Laboratory parameters indicative of toxicity did not differ between patients with polyarticular and systemic JRA and the number of adverse events reported was low. Underlying disease did not appear to predict improvement. Conclusion: Etanercept appeared to improve functional status, emotional well-being, quality of life and activity level with minimal toxicity in patients with polyarticular and systemic JRA

28. RONCHEZEL MV, HACBARTH ET, LEN CA, TERRERI MT, ANDRADE LE, HILARIO MO: Low density neutrophils in patients with juvenile idiopathic arthritis. J Investig Allergol Clin Immunol 13:2 103-107, 2003
    Organism: Pediatric Rheumatology Unit, Department of Pediatrics, Universidade Federal de Sao Paulo-Escola Paulista de Medicina, Sao Paulo, BrazilFAU - Ronchezel, M V
    Abstract: OBJECTIVES: (1) To study the correlation among conventional clinical and laboratory parameters and the relation between the number of lymphocytes and neutrophils (L/N) in cell suspensions from peripheral blood of patients with juvenile idiopathic arthritis (JIA). (2) To evaluate the L/N relation of JIA patients after an 8 year follow-up period. METHODS: Fifty-one JIA patients (25 female, disease course: 19 systemic, 15 polyarticular, 17 pauciarticular) were enrolled in the study. To measure the L/N relation, we used Boyum's method: The leucocyte separation was done by centrifugation of peripheral blood on Ficoll-Hypaque (FH) gradient, and the number of lymphocytes, monocytes, and neutrophils in 500 cells was determined. The following clinical and laboratory parameters were evaluated: disease activity, number of active and limited joints, functional capacity, erythrocyte sedimentation rate (ESR), and C reactive protein (CRP). Twenty-four healthy children were used as controls. We also studied 13/51 patients from our Pediatric Rheumatology Unit who had been evaluated by the same method 8 years before. RESULTS: We observed the lowest L/N relation in patients with active disease, especially those with polyarticular course. A statistical correlation was also observed with the acute-phase reactants (ESR and CRP, p < 0.05). The majority of patients who had presented a low L/N relation at the first evaluation (8 years before) had a worse outcome. CONCLUSION: The measure of L/N relation from peripheral blood could be used as an auxiliary tool in the assessment of the activity and outcome of JIA patients, especially at disease onset

29. RUBBERT-ROTH A, PERNIOK A: Treatment of patients with rheumatoid arthritis with the interleukin-1 receptor antagonist Anakinra (Kineret(R))
    DER INTERLEUKIN-1-REZEPTORANTAGONIST ANAKINRA (KINERET(R)) IN DER BEHANDLUNG MIT RHEUMATOIDER ARTHRITIS. Zeitschrift fur Rheumatologie (Germany ) 62:4 367-377, 2003
    Abstract: New treatment strategies in rheumatoid arthritis are targeted to interfere with critical mediators of inflammation. Proinflammatory cytokines like IL-1beta and TNFa play a crucial role in induction and maintenance of synovitis, pannus formation and bone and cartilage destruction. Within a few years, these morphological changes may lead to joint destruction and consecutively to functional impairment. Since April 2002 a recombinant human interleukin-1 receptor antagonist (Anakinra) is available in Germany for treatment of patients with rheumatoid arthritis. Anakinra (Kineret(R)) is approved for therapy in combination with methotrexate and should be applied according to guidelines established by the German Rheumatology Society for the use of biologicals in treatment of patients with rheumatoid arthritis. The approval of anakinra as a new therapeutic is based on data obtained in large multicenter, placebo-controlled, and randomised trials in comparison to placebo. Treatment of Anakinra as monotherapy or in combination with methotrexate lead to significant improvement of signs and symptoms of disease as measured by the ACR 20 (or more) response and was associated with a slower radiographic progression with regard to joint space narrowing and development of erosions. Anakinra showed a favourable safety profile with injection side reactions as the predominant side effect that occurs in 70% of patients usually after 10-12 days of treatment and that are mostly mild to moderate and self-limiting. Patients with previous pneumonia or other risk factors for pulmonary infections such as chronic obstructive lung disease seem to show a slightly increased risk of developing infectious complications of the bronchopulmonary system while being on anakinra and should be monitored appropriately. Combining IL-1ra treatment with the use of anti-TNF agents showed an increased risk of infectious complications in clinical studies and is not recommended at present. Studies are currently assessing the use of anakinra for treatment of other rheumatic diseases like psoriatic arthritis, juvenile arthritis or spondylarthropathy

30. SINGH JA, WILLIAMS CB, MCALISTER WH: Talo-patello-scaphoid osteolysis, synovitis, and short fourth metacarpals in sisters: A new syndrome? American Journal of Medical Genetics (United States ) 121 A:2 118-125, 2003
    Abstract: Osteolysis syndromes are characterized by resorption of affected bones with associated swelling and pain. Various forms of multicentric osteolysis syndromes including autosomal dominant and recessive carpal-tarsal osteolysis, Torg, Franc(cedil)ois, Whyte-Hemingway, Hajdu-Cheney, Winchester, and other forms have been described. Most present in pre-school years with extensive involvement and destruction of multiple bones. We present a sister-pair, both of whom presented in early teenage, i.e., 13 and 15.5 years, respectively, with bilateral ankle, knee, and later, wrist pain. Radiological examination revealed bilateral osteolysis of tali, scaphoids, and patellae, and short fourth metacarpals in both sisters. Further investigation revealed absence of renal involvement, a normal excretion of amino acids, mucopolysaccharides and oligosaccharides, and presence of chronic synovitis in both sisters. Both parents and a younger brother were without radiographic or clinical evidence of the disease and there was no history of consanguinity. Thus, our sister-pair presented with the same carpal and tarsal bone involvement at a much later age, with evidence of chronic synovitis, along with short fourth metacarpals (brachydactyly type E changes) and without renal disease, suggesting a new syndrome with probable autosomal recessive inheritance. (c) 2003 Wiley-Liss, Inc

31. WAGNER JL, CHANEY JM, HOMMEL KA, PAGE MC, MULLINS LL, WHITE MM, JARVIS JN: The influence of parental distress on child depressive symptoms in juvenile rheumatic diseases: the moderating effect of illness intrusiveness. J Pediatr Psychol 28:7 453-462, 2003
    Organism: Department of Psychology, Oklahoma State University, 215 North Murray Hall, Stillwater, OK 74078, USA stern@okstateeduFAU - Wagner, Janelle L
    Abstract: OBJECTIVE: To examine the role of children's illness-related cognitive appraisals in the parent-child adjustment relationship in a sample of children and adolescents with juvenile rheumatic disease (JRD). Specifically, we tested the moderating effect of children's perceived illness-induced barriers (i.e., illness intrusiveness) in the parent distress-child depressive symptom relationship. METHODS: Participants were 45 children and adolescents (ages 9-17) diagnosed with JRD. Children completed measures of depressive symptoms (Children's Depression Inventory), functional disability (Juvenile Arthritis and Functional Assessment Report), and illness intrusiveness (Illness Intrusiveness Scale-adapted for children); parents completed a brief measure of global distress (Brief Symptom Inventory). The pediatric rheumatologist provided functional disability ratings following a routine physical exam. RESULTS: Both increased parental distress and child illness intrusiveness were associated with greater child depressive symptoms. Direct effects were qualified by a significant Parent Distress x Illness Intrusiveness interaction. The influence of general parental distress on child depressive symptoms was enhanced under conditions of increased child-reported illness intrusiveness. CONCLUSIONS: Results support transactional conceptualizations of child adjustment to chronic illness. Findings also emphasize the need to examine the interaction of parent and child variables, particularly cognitive appraisals, in child adjustment. Results and treatment implications for children with JRD are discussed in terms of reinforcement theories of depression

32. WOO P: Recent advances in the management of juvenile idiopathic arthritis. Current Paediatrics (United Kingdom ) 13:5 335-340, 2003
    Abstract: The medical management of polyarthritis in the different subtypes of juvenile idiopathic arthritis has been revolutionized over the past decade. The use of methotrexate has undergone extensive clinical trials and post-marketing monitoring. The safe and effective range of dosages has been defined. Other conventional disease-modifying drugs may also improve those with methotrexate-resistant arthritis. The outcome and quality of life in approximately 60% of children with arthritis has been substantially improved as a result. The advent of biologics has been a further advance towards a new generation of novel therapies aimed at specific inflammatory molecules found to be relevant in different diseases. The use of anti-tumour necrosis factor therapy in those who fail on methotrexate further decreases the number of children with chronic inflammation and undesirable secondary effects such as growth failure, osteoporosis and deformities. (c) 2003 Elsevier Ltd. All rights reserved

33. YOKOTA S: Interleukin 6 as a therapeutic target in systemic-onset juvenile idiopathic arthritis. Curr Opin Rheumatol 15:5 581-586, 2003
    Organism: Department of Pediatrics, Yokohama City University School of Medicine, Kanagawa, Japan syokota@medyokohama-cuacjpFAU - Yokota, Shumpei
    Abstract: PURPOSE OF REVIEW: Systemic-onset juvenile idiopathic arthritis is a severe and steroid-dependent disease that sometimes progresses to a fatal disease, macrophage activation syndrome. The investigation of proinflammatory cytokine levels revealed the increases of interleukin 6 in serum of systemic-onset disease. To avoid the disease progression and the adverse events of high-dose corticosteroids, it might be a reasonable treatment strategy to inhibit the formation of interleukin 6/interleukin 6 receptor complex to block the binding to gp130 receptor, a biologically active receptor for interleukin 6. RECENT FINDINGS: Continuously elevated levels of interleukin 6 in serum may play an important role in manifesting the clinical symptoms and signs of systemic-onset juvenile idiopathic arthritis, including spiking fever, rash, arthritis, and serositis. The characteristic fever spikes parallel interleukin 6 levels. A long-term exposure of high levels of interleukin 6 brings children severe growth impairment, which was strongly suggested by the recent establishment of interleukin 6 transgenic mice. SUMMARY: This review will provide the evidences of the relation between the imbalance of interleukin 6 homeostasis and systemic-onset juvenile idiopathic arthritis. Also reviewed will be the author's recent trials of anti interleukin 6 receptor antibody, named temporally as MRA, for children with acute systemic disease intractable to long-term, high-dose, corticosteroid therapy. MRA would be a therapeutic modality for children with systemic-onset juvenile idiopathic arthritis intractable to high-dose corticosteroids

34. ZAK M, FLEDELIUS H, PEDERSEN FK: Ocular complications and visual outcome in juvenile chronic arthritis: A 25-year follow-up study. Acta Ophthalmologica Scandinavica 81:3 211-215, 2003
    Abstract: Objective: Assessment of longterm ophthalmic outcome in juvenile chronic arthritis (JCA) with emphasis on visual acuity and identification of disease-related parameters associated with rheumatic eye affection. Material: Sixty-five adults (52 females, 13 males) with a history of or still active JCA were assessed an average of 26.7 years after disease onset. Methods: Cross-sectional, longterm, follow-up study including complete ophthalmological and rheumatological examinations. Results: Evidence of ocular complications was found in 13 subjects (20%): 10 had had recurrent iritis, two band keratopathy, and one diplopia due to rheumatoid eye muscle involvement. The three single eyes with poor sight (< 0.1) were all in the complication subgroup. Binocularly, all but one patient scored at least 6/9 as best corrected visual acuity; one, however, had severe glaucoma-impaired visual fields. The refractive range was -8.12 to +6.0 D. There were no cases of keratoconjunctivitis sicca. Iritis was associated with early disease onset (p = 0.02), longer disease duration (p = 0.02) and a positive antinuclear antibodies (ANA) (p = 0.02). Conclusion: Ophthalmic complications were recorded in 20% of the study group, primarily in ANA positive patients with pauciarticular onset JCA. In addition to the two patients with severely affected bilateral visual status (3%), one of the 65 patients had acquired unilateral blindness. Half of the complications were late in that they were first recorded after the age of 16 years. Otherwise, the findings were in keeping with other studies of visual prognosis using non-selected series

35. ZHANG Y: Animal models of inflammatory spinal and sacroiliac joint diseases. Rheum Dis Clin North Am 29:3 631-645, 2003
    Organism: Department of Neurology, University of California-Irvine, 100 Irvine Hall, Irvine, CA 92697-4275, USA zhangy@ucieduFAU - Zhang, Yiping
    Abstract: Many cartilage matrix proteins or domains such as collagen types II, IX, and XI, GP39, AG1, VG1, and LP are potential antigens that might induce polyarthritis in susceptible animals (Table 1). Ordinarily, spondylitis is not a feature of polyarthritis induced with collagen types II, IX, and XI, GP39, cartilage matrix protein (matrilin-1) and cartilage LP. It seems that only the proteoglycans aggrecan and versican are capable of inducing sacroiliitis and spondylitis. Both molecules are structural proteins in intervertebral discs. Moreover, the arthritogenic or spondylitogenic epitopes of both molecules have been localized to the homologous N-terminal G1 globular domains. This region of versican and aggrecan is highly conserved, with 52% identity of amino acids. The homology is seen exclusively in the G1 domain and is concentrated between residues 115 and 332 (AG1 numbering) near the natural cleavage DIPEN site of aggrecan [84, 85]. Extra-articular pathology is often seen in rheumatic diseases, especially in AS. Other tissues, such as the sclera of the eye [86] and the media of the arteries [86, 87], also contain type II collagen, AG1, VG1, and LP, and versican is present in the central and peripheral nervous systems. Thus, there is the potential for an immune response against cartilage G1 and LP to be directed against related structures in extra-articular tissues. The presence of versican in the tendon and trochlea of the human superior oblique muscle might account for the occurrence of transient attacks of acquired Brown syndrome in patients with juvenile and adult forms of chronic RA [88]. Thus, it will be interesting to determine whether or not extra-articular expression of these cartilage proteins is closely related to extra-articular pathogenic expression in rheumatic diseases. Uveitis develops in VG1-immunized BALB/c mice, which is not seen in AG1-, and LP-treated animals. There is evidence that aggrecan and LP are also localized at these sites in the eye, but only immunity to versican can induce uveitis. In sacroiliitis and enthesitis of AS patients, the inflammation is associated with chondrometaplasia. In versican-induced sacroiliitis, replacement of cartilage by bone is seen with relatively little inflammation, somewhat resembling the situation in AS (Fig. 2). Versican can also stimulate chondrocyte proliferation [43]. Three conserved domains of human cartilage matrix molecules, namely VG1, AG1, and LP, show considerable homology [77, 79, 80, 89], and each is capable of inducing a unique inflammatory arthritis in BALB/c mice, with VG1 inducing only spondylitis [65], LP inducing peripheral arthritis with no spondylitis [90], and AG1 inducing axial and peripheral arthritis [66, 91]. It remains a mystery why such similar molecules cause different pathology in different target tissues. The exact immunopathogenic mechanisms deserve further study