Bibliography June 2008

1. BEHRENS EM, FINKEL TH, BRADFIELD JP, KIM CE, LINTON L, CASALUNOVO T, FRACKELTON EC, SANTA E, OTIENO FG, GLESSNER JT, CHIAVACCI RM, GRANT SFet HAKONARSON H: Association of the TRAF1-C5 locus on chromosome 9 with juvenile idiopathic arthritis, Arthritis Rheum., Vol. 58(7), 2206-2207., 2008
   Organism:The Children's Hospital of Philadelphia, Philadelphia, PA, USAFAU - Behrens, Edward M
   Abstract:

2. BILSEL N, GOKCE A, KESMEZACAR H, MUMCUOGLU Eet OZDOGAN H: [Long-term results of total hip arthroplasty in patients with juvenile rheumatoid arthritis.], Acta Orthop.Traumatol.Turc., Vol. 42(2), 119-124., 2008
   Organism:Department of Orthopedics and Traumatology (Ortopedi ve Travmatoloji Anabilim Dali), Cerrahpasa Medicine Faculty of Istanbul University, Istanbul, Turkey
   Abstract:OBJECTIVES: We evaluated the long-term results of total hip arthroplasty (THA) in patients with juvenile rheumatoid arthritis (JRA). METHODS: The study included 37 hips of 23 patients (22 females, 1 male; mean age 22 years; range 17 to 30 years) who underwent THA for hip degeneration secondary to JRA. All arthroplasties were performed through an anterolateral approach by the same senior surgeon. The mean body surface of the patients was 1.5 m (range 1.1 to 1.7 m) and the mean symptom duration to surgery was 12 years (range 7 to 16 years). Twenty-three hips received cemented, 14 hips received hybrid prostheses. In seven hips with an extremely narrow femoral medulla and shallow acetabulum, a CDH prosthesis was used. The hips were evaluated using the Harris hip score. Prosthetic loosening and displacement and heterotopic bone formation were assessed on follow-up radiographs. The mean follow-up period was 135 months (range 58 to 212 months). RESULTS: The mean Harris hip score increased from 27.2 (range 11 to 69) to 79.5 (range 37 to 87) postoperatively. At final follow-ups, all the patients were satisfied with the outcome and were able to walk without support. Three hips (8.1%; 3 patients) required revision. The overall Kaplan-Meier implant survival rate was 86.5%. There were no significant correlations between the Harris hip score and radiographic loosening and the presence of calcification around the prosthesis. Heterotopic bone formation of grade I was observed in 17 hips (46%). CONCLUSION: Even though it is performed at young ages, THA considerably improves quality of life of patients with JRA having hip joint involvement and has a comparable implant survival

3. BOSCO MC, DELFINO S, FERLITO F, BATTAGLIA F, PUPPO M, GREGORIO A, GAMBINI C, GATTORNO M, MARTINI Aet VARESIO L: Hypoxic synovial environment and expression of macrophage inflammatory protein 3gamma/CCL20 in juvenile idiopathic arthritis, Arthritis Rheum., Vol. 58(6), 1833-1838., 2008
   Organism:G Gaslini Institute, Genoa, Italy mcbosco1@virgilioitFAU - Bosco, Maria Carla
   Abstract:OBJECTIVE: Synovial inflammation is a major determinant of juvenile idiopathic arthritis (JIA) pathogenesis and is mediated by local chemokine secretion. Monocytic cells are an important source of chemokines. The purpose of this study was to investigate expression of CCL20, a macrophage inflammatory protein, in synovial fluid (SF) and SF-derived monocytic cells from JIA patients and its regulation by hypoxia, a common feature of the inflamed synovial environment. METHODS: Mononuclear cells and monocytic cells were isolated from paired SF and peripheral blood (PB) samples from JIA patients and were maintained in a hypoxic environment or subjected to reoxygenation. CCL20 concentrations in SF, PB, and culture supernatants were measured by enzyme-linked immunosorbent assay. CCL20 expression was assessed in both freshly purified and cultured cells by reverse transcriptase-polymerase chain reaction and immunocytochemistry. Hypoxia-inducible factor 1alpha (HIF-1alpha) and HIF-2alpha were detected in the synovial tissue and cells of JIA patients by immunohistochemistry and Western blotting. RESULTS: CCL20 concentrations were significantly higher in SF compared with PB samples (P < 0.0001). SF mononuclear cells, but not matched PB mononuclear cells, constitutively expressed CCL20 messenger RNA. The SF monocytic cell fraction produced higher amounts of CCL20 than did SF lymphocytes, and CCL20 expression was associated with HIF positivity. Reoxygenation abrogated HIF and CCL20 expression, which was maintained in SF monocytic cells exposed to prolonged hypoxia. CONCLUSION: CCL20 is released into the SF of JIA patients, and SF monocytic cells are a major source of this chemokine. The hypoxic synovial microenvironment may directly contribute to the persistent inflammation associated with JIA by increasing CCL20 production by SF monocytic cells, thus representing a potential therapeutic target

4. BRAUN-MOSCOVICI Y, MARKOVITS D, ROZIN A, TOLEDANO K, NAHIR AMet BALBIR-GURMAN A: Anti-tumor necrosis factor therapy: 6 year experience of a single center in northern Israel and possible impact of health policy on results, Isr.Med.Assoc.J., Vol. 10(4), 277-281., 2008
   Organism:B Shine Department of Rheumatology, Rambam Medical Health Care Campus, Technion, Haifa, Israel y_braun@rambamhealthgovilFAU - Braun-Moscovici, Yolanda
   Abstract:BACKGROUND: Infliximab and etanercept have been included in the Israeli national list of health services since 2002 for rheumatoid arthritis and juvenile idiopathic arthritis, and since 2005 for psoriatic arthritis and ankylosing spondylitis. The regulator (Ministry of Health and health funds) mandates using fixed doses of infliximab as the first drug of choice and prohibits increased dosage. For other indications (e.g., vasculitis), anti-tumor necrosis factor therapy is given on a "compassionate" basis in severe refractory disease. OBJECTIVES: To describe our experience with anti-TNF therapy in a single tertiary referral center in northern Israel and to analyze the impact of the national health policy on the results. METHODS: We reviewed the medical records of patients who received anti-TNF therapy in our institution, and analyzed demographic data, diagnosis, clinical and laboratory features, previous and current therapies, and anti-TNF treatment duration and side effects. RESULTS: Between 2001 and 2006, 200 patients received anti-TNF therapy for rheumatoid arthritis (n = 108), juvenile idiopathic arthritis (n = 11), psoriatic arthritis (n = 37), ankylosing spondylitis (n = 29), adult Still's disease (n = 4), overlap disease (RA and scleroderma or polymyositis, n = 6), temporal arteritis (n = 1), polyarteritis nodosa (n = 1), dermatomyositis (n = 1), amyloidosis secondary to RA (n = 1) and Wegener's granulomatosis (n = 1). Forty percent of RA patients discontinued the first anti-TNF agent due to side effects or insufficient response. Higher sedimentation rate and lower or negative rheumatoid factor predicted better response to therapy among RA patients. AS and PS patients had a better safety and efficacy profile. Severe infections occurred in 2% of patients. All eight patients who presented lung involvement as part of their primary rheumatic disease remained stable or improved. A significant improvement was achieved in all six patients with overlap disease. CONCLUSION: Our daily practice data are generally in agreement with worldwide experience. The 'deviations' might be explained by the local health policy at that time. The impact of health policy and economic and administrative constraints should be taken into account when analyzing cohort daily practice data

5. CHAN Y, TANG WY, LAM WY, LOO SK, LI SP, AU AW, LEUNG WY, KWAN CKet LO KK: A cluster of chilblains in Hong Kong, Hong.Kong.Med.J., Vol. 14(3), 185-191., 2008
   Organism:Department of Medicine and Geriatrics, Tuen Mun Hospital, Tuen Mun, Hong KongFAU - Chan, Y
   Abstract:OBJECTIVE: To report a recent clustering of chilblain cases in Hong Kong. DESIGN: Case series. SETTING: A regional hospital and a social hygiene clinic in the New Territories West, Hong Kong. PATIENTS: Patients with a clinical diagnosis of chilblains in February 2008. RESULTS: Eleven patients with chilblains were identified; seven (64%) gave an antecedent history of prolonged exposure to cold. They all presented with erythematous or dusky erythematous skin lesions affecting the distal extremities, especially fingers and toes. Laboratory tests revealed elevated antinuclear antibodies titres in two, positive rheumatoid factor in two, presence of cold agglutinins in one, and a raised anti-DNA titre (>300 IU/mL) in one. Skin biopsies were performed in six patients, four of them showed typical histopathological features of chilblains. In the patient with systemic lupus erythematosus, features of vasculitis were suspected, and in the one with pre-existing juvenile rheumatoid arthritis, there were features of livedo vasculitis. In 10 (91%) of the patients, the skin lesions had resolved when they were last assessed (at the end of March 2008), but had persisted in the patient who had pre-existing systemic lupus erythematosus. CONCLUSION: The recent clustering of chilblains was possibly related temporally to the prolonged cold weather at the end of January to mid-February. In our series, most of the patients developed chilblains as an isolated condition and resolved spontaneously within a few weeks. Laboratory tests and skin biopsies for chilblains are not necessary, unless the condition persists, the diagnosis in doubt or an underlying systemic disease is suspected

6. DAY TG, RAMANAN AV, HINKS A, LAMB R, PACKHAM J, WISE C, PUNARO Met DONN RP: Autoinflammatory genes and susceptibility to psoriatic juvenile idiopathic arthritis, Arthritis Rheum., Vol. 58(7), 2142-2146., 2008
   Organism:University of Manchester, Manchester, UKFAU - Day, T G
   Abstract:OBJECTIVE: To investigate the association of NLRP3, NOD2, MEFV, and PSTPIP1, genes that cause 4 of the autoinflammatory hereditary periodic fever syndromes (HPFS), with juvenile idiopathic arthritis (JIA). METHODS: Fifty-one single-nucleotide polymorphisms (SNPs) across the 4 loci were investigated using MassArray genotyping in 950 Caucasian patients with JIA living in the UK and 728 ethnically matched healthy controls. RESULTS: Prior to Bonferroni correction for multiple testing, significant genotype associations between 6 SNPs in MEFV and JIA were observed and, in subgroup analysis, associations between 12 SNPs across all 4 loci and the subgroup of patients with psoriatic JIA were found. After Bonferroni correction for multiple testing, 2 genotype associations remained significant in the subgroup of patients with psoriatic JIA (MEFV SNP rs224204 [corrected P = 0.025] and NLRP3 SNP rs3806265 [corrected P = 0.04]). CONCLUSION: These findings support the use of monogenic loci as candidates for investigating the genetic component of complex disease and provide preliminary evidence of association between SNPs in autoinflammatory genes and psoriatic JIA. Our findings raise the interesting possibility of a shared disease mechanism between the HPFS and psoriatic JIA, potentially involving abnormal production of interleukin-1beta

7. DUZOVA Aet BAKKALOGLU A: Central nervous system involvement in pediatric rheumatic diseases: current concepts in treatment, Curr.Pharm.Des., Vol. 14(13), 1295-1301., 2008
   Organism:Department of Pediatrics, Pediatric Nephrology and Rheumatology Unit, Hacettepe University Faculty of Medicine, Ankara, TurkeyFAU - Duzova, Ali
   Abstract:Central nervous system (CNS) manifestations are not rare in pediatric rheumatic diseases. They may be a relatively common feature of the disease, as in systemic lupus erythematosus (SLE) and Behcet's disease. Direct CNS involvement of a systemic rheumatic disease, primary CNS vasculitis, indirect involvement secondary to hypertension, hypoxia and metabolic changes, and drug associated adverse events may all result in CNS involvement. We have reviewed the CNS manifestations of SLE, Behcet's disease, Henoch-Schonlein purpura, polyarteritis nodosa, juvenile idiopathic arthritis, juvenile ankylosing spondylitis, familial Mediterranean fever, scleroderma, sarcoidosis, Wegener's granulomatosis, Takayasu's arteritis, CINCA syndrome, Kawasaki disease, and primary CNS vasculitis; and adverse CNS effects of anti-rheumatic drugs in pediatric patients. The manifestations are diverse; ranging from headache, seizures, chorea, changes in personality, depression, memory and concentration problems, cognitive impairment, cerebrovascular accidents to coma, and death. The value of cerebrospinal fluid (CSF) examination (pleocytosis, high level of protein), auto-antibodies in serum and CSF, electroencephalography, neuroimaging with computerized tomography, magnetic resonance imaging, SPECT, PET, and angiography depends on the disease. Brain biopsy is gold standard for the diagnosis of CNS vasculitis, however it may be inconclusive in 25% of cases. A thorough knowledge of the rheumatic diseases and therapy-related adverse events is mandatory for the management of a patient with rheumatic disease and CNS involvement. Severe CNS involvement is associated with poor prognosis, and high mortality rate. High dose steroid and cyclophosphamide (oral or intravenous) are first choice drugs in the treatment; plasmapheresis, IVIG, thalidomide, and intratechal treatment may be valuable in treatment-resistant, and serious cases

8. EHRMANN FD, BERNATSKY S, ABRAHAMOWICZ M, ROY Y, XIAO Y, HAGGERTY J, LEFFONDRE K, TOUSIGNANT Pet DUFFY CM: Consultation with an arthritis specialist for children with suspected juvenile rheumatoid arthritis: a population-based study, Arch.Pediatr.Adolesc.Med., Vol. 162(6), 538-543., 2008
   Organism:Faculte de Medecine, Ecole de Readaptation, Universite de Montreal, CP 6128, Succursale Centre-ville, Montreal, QC H3C 3J7, Canada Debbiefeldman@umontrealcaFAU - Ehrmann Feldman, Debbie
   Abstract:OBJECTIVES: To describe consultation with an arthritis specialist because of suspected new-onset juvenile rheumatoid arthritis (JRA) and to determine factors associated with prompt consultation. DESIGN: Retrospective cohort study. SETTING: Physician reimbursement administrative data were obtained for all children aged 16 years or younger in the Province of Quebec (Canada). PARTICIPANTS: Suspected new-onset cases of JRA in 2000 were defined by a physician visit because of JRA, providing there had been no such claims in the preceding 3 years. MAIN EXPOSURE: First JRA diagnosis made by a non-arthritis specialist. MAIN OUTCOME MEASURES: First consultation with an arthritis specialist subsequent to diagnosis by a non-arthritis specialist and time to first consultation with an arthritis specialist. RESULTS: Of 352 children and adolescents with suspected new-onset JRA identified by non-arthritis specialists, 159 (45.2%) were subsequently seen by an arthritis specialist. Mean (SD) time to consultation for those seen was 115.3 (213.8) days (median, 28 days). Younger children were more likely to obtain care from an arthritis specialist compared with those having JRA first diagnosed by a general practitioner. CONCLUSION: Most patients with suspected new-onset JRA do not obtain prompt care from an arthritis specialist. Further research and action should focus on this issue so that outcomes may be optimized

9. GALEOTTI L, ADRIAN K, BERG S, TARKOWSKI Aet BOKAREWA M: Circulating survivin indicates severe course of juvenile idiopathic arthritis, Clin.Exp.Rheumatol., Vol. 26(2), 373-378., 2008
   Organism:Rheumatology Unit of Pediatrics, Pedro de Elizalde Hospital, Buenos Aires, ArgentinaFAU - Galeotti, L
   Abstract:BACKGROUND: Survivin is an anti-apoptotic protein that has been recently suggested as a predictive marker of joint destruction in adult rheumatoid arthritis. We assessed the presence of extracellular survivin in patients with juvenile idiopathic arthritis (JIA). METHODS: Survivin levels were assessed in the circulation of 46 patients with JIA and in the age- and gender-matched controls (n=46) having no inflammatory disease, by ELISA. Survivin levels were analyzed with respect to the onset type and the activity of the joint disease. The intensity of inflammation and cartilage turnover was measured as levels of IL-6, serum amyloid A protein (SAA), and cartilage oligomeric matrix protein (COMP), respectively. RESULTS: The levels of extracellular survivin were significantly higher in JIA compared to the controls (p=0.0002). High levels of survivin (above mean + 2SD of the controls) were detected in 8/46 (17% JIA patients. High survivin expression was associated with polyarticular onset, active phase of arthritis. In contrast, survivin was neither related to the levels of IL-6, SAA, nor to COMP. CONCLUSION: Circulating survivin is expressed in a significant group of patients with JIA being associated to a severe course of the disease. It may be potentially used to select children with unfavorable prognosis of JIA who are in need of active pharmacologic treatment

10. GHOSH JB, GUPTA Det CHATTOPADHYAY N: Systemic onset juvenile idiopathic arthritis--its unusual presentation, Indian J.Pediatr., Vol. 75(4), 400-402., 2008
    Organism:Department of Pediatrics, Institute of Post Graduate Medical Education and Research Hospital, Kolkata, India jbghosh@yahoocomFAU - Ghosh, J B
    Abstract:We report a case of systemic onset juvenile idiopathic arthritis (SOJIA), the manifestations of which started with fever and skin rash followed by arthritis within neonatal age. Such presentation is extremely rare in the newborn. After exclusion of closely mimicking conditions like congenital infections, neonatal onset multisystem inflammatory disease (NOMID), neonatal; lupus erythematosus (NLE) diagnosis of SOJIA may be entertained even in a neonate where arthritis, fever and rash are the presenting features

11. GILLIAM BE, CHAUHAN AK, LOW JMet MOORE TL: Measurement of biomarkers in juvenile idiopathic arthritis patients and their significant association with disease severity: a comparative study, Clin.Exp.Rheumatol., Vol. 26(3), 492-497., 2008
    Organism:Division of Adult and Pediatric Rheumatology, Department of Internal Medicine and Pediatrics, Saint Louis University School of Medicine, Saint Louis, MO, USAFAU - Gilliam, B E
    Abstract:OBJECTIVE: To evaluate in juvenile idiopathic arthritis (JIA) patients a biomarker panel of anti-cyclic citrullinated peptide (anti-CCP) antibodies, cartilage oligomeric matrix protein (COMP), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), IgM rheumatoid factor (RF), IgG RF, and IgA RF and compare to the presence of joint erosions (JE), joint space narrowing (JSN), and synovitis in order to evaluate aggressive disease. METHODS: Sixty-eight JIA patients (19 RF positive polyarthritis, 23 RF negative polyarthritis, 17 persistent oligoarthritis, and 9 systemic-onset) were evaluated using the biomarker panel and compared to 18 healthy controls. All RF isotypes, anti-CCP antibodies, and COMP were measured by enzyme-linked immunosorbent assays (ELISA). Statistically significant differences and associations were assessed for each biomarker in relation to JE, JSN, and synovitis. Multiple regression analysis was used to find the variables associated with joint damage and synovitis. RESULTS: Patients with JE and JSN had significantly elevated levels of IgA RF, IgM RF, and anti-CCP antibodies. COMP levels were higher in early disease, but also later in disease in patients with no JE or JSN. ESR, CRP, and IgA RF were significantly elevated in patients with active synovitis. Regression analysis showed IgM RF and disease duration to be associated with JE and JSN. Anti-CCP antibodies and COMP were also associated with JSN. CRP and IgA RF were associated with synovitis. CONCLUSION: Our findings demonstrate the importance of measuring IgM RF and IgA RF by ELISA and anti-CCP antibodies by ELISA, in addition to COMP in the assessment of JIA patients to determine severity of disease

12. HERLIN T: [Biological therapy treatment of juvenile idiopathic arthritis], Ugeskr.Laeger., Vol. 170(24), 2105-2108., 2008
    Organism:Arhus Universitetshospital, Skejby, Borneafdelingen, Arhus N therlin@dadlnetdkFAU - Herlin, Troels
    Abstract:In recent years the treatment of juvenile idiopathic arthritis (JIA) has undergone marked changes. There is substantial evidence that inhibitors of tumor necrosis factor alpha (TNFalpha) like etanercept, infliximab and adalimumab show significant efficacy when standard therapy fails, and long-term tolerability is fairly good. Patients with systemic JIA do not respond well to treatment with TNF inhibitors, but they may benefit from treatment with IL-1 and IL-6 receptor antagonists. Our knowledge is still limited regarding which patients respond to a specific biological therapy

13. JANICKE DM, HARMAN JS, KELLEHER KJet ZHANG J: Psychiatric diagnosis in children and adolescents with obesity-related health conditions, J.Dev.Behav.Pediatr., Vol. 29(4), 276-284., 2008
    Organism:Departments of Clinical and Health Psychology, University of Florida, Gainesville, Florida 32610-0165, USA djanicke@phhpufleduFAU - Janicke, David M
    Abstract:OBJECTIVE: Childhood obesity is linked with a number of problematic health conditions. While data suggest that children who are obese are at increased risk of psychosocial distress relative to nonobese peers, there are limited data outlining the rates of psychiatric diagnoses in children with obesity-related health conditions such as type 2 diabetes and the metabolic syndrome. METHODS: This study used Medicaid claims data from the State of Florida to compare the rates of psychiatric diagnoses for children with obesity-related health conditions, aged 5 to 18 years, to those of children with comparison chronic health conditions. RESULTS: Overall, 35% of children with an obesity-related diagnosis had a psychiatric diagnosis. While controlling for age, gender, and race, youths with type 2 diabetes, the metabolic syndrome, and dyslipidemia had higher rates of International Classification of Disease, Ninth Revision (ICD-9) psychiatric diagnoses than children with cystic fibrosis, sickle cell disease, and juvenile rheumatoid arthritis (p < .001), but similar to those of children with asthma. Non-Hispanic white children with an obesity-related health condition had greater odds of receiving a psychiatric diagnosis than African American (odds ratio [OR] = 0.54, p < .001) or Hispanic (OR = 0.41, p < .001) children. Males and females differed in rates of externalizing and internalizing diagnoses. CONCLUSIONS: The data suggest that children with an obesity-related health condition have higher rates of internalizing and externalizing mental health conditions relative to children with other chronic health conditions. Prospective, longitudinal research is needed to further confirm these findings and examine factors that affect this association and potential impacts on the health care system

14. JOHNSEN AK, PLENGE RM, BUTTY V, CAMPBELL C, DIEGUEZ-GONZALEZ R, GOMEZ-REINO JJ, SHADICK N, WEINBLATT M, GONZALEZ A, GREGERSEN PK, BENOIST Cet MATHIS D: A broad analysis of IL1 polymorphism and rheumatoid arthritis, Arthritis Rheum., Vol. 58(7), 1947-1957., 2008
    Organism:Joslin Diabetes Center, Harvard Medical School, Boston, Massachusetts, USAFAU - Johnsen, Alyssa K
    Abstract:OBJECTIVE: It has been suggested that polymorphisms in IL1 are correlated with severe and/or erosive rheumatoid arthritis (RA), but the implicated alleles have differed among studies. The aim of this study was to perform a broad and well-powered search for association between allelic polymorphism in IL1A and IL1B and the susceptibility to or severity of RA. METHODS: Key coding and regulatory regions in IL1A and IL1B were sequenced in 24 patients with RA, revealing 4 novel single-nucleotide polymorphisms (SNPs) in IL1B. These and a comprehensive set of 24 SNPs tagging most of the underlying genetic diversity were genotyped in 3 independent RA case-control sample sets and 1 longitudinal RA cohort, totaling 3,561 patients and 3,062 control subjects. RESULTS: No fully significant associations were observed. Analysis of the discovery case-control sample sets indicated a potential association of IL1B promoter region SNPs with susceptibility to RA (for RA3/A, odds ratio [OR] 1.27, P = 0.0021) or with the incidence of radiographic erosions (for RA4/C, OR 1.56, P = 0.036), but these findings were not replicated in independent case-control samples. No association with rheumatoid factor, anti-cyclic citrullinated peptide, or the Disease Activity Score in 28 joints was found. None of the associations previously observed in other studies were replicated here. CONCLUSION: In spite of a broad and highly powered study, we observed no robust, reproducible association between IL1A/B variants and the susceptibility to or severity of RA in white individuals of European descent. Our results provide evidence that, in the majority of cases, polymorphism in IL1A and IL1B is not a major contributor to genetic susceptibility to RA

15. MOORTHY LN, PETERSON MG, HARRISON MJ, ONEL KBet LEHMAN TJ: Physical function assessment tools in pediatric rheumatology, Pediatr.Rheumatol.Online.J., Vol. 6, 9, 2008
    Organism:Robert Wood Johnson Medical School-UMDNJ, Dept, of Pediatrics, Division of Rheumatology, New Brunswick, NJ 08903, USA LNMOORTHY@MACCOMFAU - Moorthy, Lakshmi Nandini
    Abstract:ABSTRACT: Pediatric rheumatic diseases with predominant musculoskeletal involvement such as juvenile idiopathic arthritis (JIA) and juvenile dermatomyositis(JDM) can cause considerable physical functional impairment and significantly affect the children's quality of life (QOL). Physical function, QOL, health-related QOL (HRQOL) and health status are personal constructs used as outcomes to estimate the impact of these diseases and often used as proxies for each other. The chronic, fluctuating nature of these diseases differs within and between patients, and complicates the measurement of these outcomes. In children, their growing needs and expectations, limited use of age-specific questionnaires, and the use of proxy respondents further influences this evaluation. This article will briefly review the different constructs inclusive of and related to physical function, and the scales used for measuring them. An understanding of these instruments will enable assessment of functional outcome in clinical studies of children with rheumatic diseases, measure the impact of the disease and treatments on their lives, and guide us in formulating appropriate interventions

16. MUSZYNSKI P, SKLADZIEN J, RERON E, STREK P, POPIELSKI L, DUTSCH-WICHEREL M, KOCON Set BARTNIK J: [Transient evoked otoacustic emission in children with juvenile idiopatic arthritis], Otolaryngol.Pol., Vol. 61(6), 972-978., 2007
    Organism:Katedra i Klinika Otolaryngologii Collegium Medicum Uniwersytetu Jagiellonskiego w KrakowieFAU - Muszynski, Piotr
    Abstract:Juvenile idiopathic arthritis (JCA) is an inflammatory systemic disease of connective tissue which etiology is still unknown. Progressive arthritis is the basic symptom, with pain, oedema, stiffness and movement impediment are typical for. Chronic process of arthritis might be accompanied by rheumatoid nodes, pericarditis, myocarditis, changes in the lungs and kidney, which appear with various frequency and indicates on systemic form of disease. The incudo-malleolar and incudo-stapedial joints are synovial in type. It should be expected that these joints might be affected by rheumatoid changes similar to those observed in joints in other parts of the body. Copeman was the first who described transient conductive hearing loss in patients with exacerbated rheumatoid process--and he called it oto-arthritis. He stressed that it was the consequence of the rheumatoid lesions in joints of ear ossicules. In adult patients with JCA in 60% of cases the perceptive hearing-loss is observed possibly because of the chronic course of the disease and its farmacological treatment. The aim of the study was the assessment of the functional state of the peripheral part of hearing organ on the basis of TEOAE. This study was preceded by examination of hearing with pure tone audiometry, speech audiometry, high frequency audiometry and impedance audiometry. The analysis of results was done in correllation to form of JCA and its activity. The research was carried out on the group of 45 children suffering from JCA; 14 boys and 31 girls between 5-18 years of age. In all children from experimental group the examination was performed in the active phase of disease process. Mean duration of the disease was 33.5 month. In all children TEOAE was obtained no matter on the form of JCA. Children with systematicus form of JCA--more aggressive type than others--have the recordings of TEOAE with small amplitude and narrow range of frequency. Those results show that rheumatoid lesions in conductive mechanism of the middle ear are insufficient for the development of the conductive hearing loss. As a results of chronic pathological process destructions of hearing organ may lead to the cochlear lesions and this way to perceptive hearing loss

17. NGUYEN-OGHALAI TU, WU H, MCNEARNEY TA, GRANGER CVet OTTENBACHER KJ: Functional outcome after stroke in patients with rheumatoid arthritis and systemic lupus erythematosus, Arthritis Rheum., Vol. 59(7), 984-988., 2008
    Organism:Division of Rheumatology, University of Texas Medical Branch, Galveston, TX 77555, USA tranguye@utmbeduFAU - Nguyen-Oghalai, Tracy U
    Abstract:OBJECTIVE: To compare outcomes following stroke rehabilitation among patients with rheumatoid arthritis (RA) or systemic lupus erythematosus (SLE) versus patients with neither RA nor SLE (non-RA/SLE). METHODS: We conducted a retrospective analysis using a national database of patients with stroke admitted to inpatient rehabilitation between 1994 and 2001. Primary outcomes were discharge disposition and functional status, rated by the Functional Independence Measure (FIM) Instrument, at discharge and at followup. The independent variable was RA or SLE. Covariates were age, sex, race/ethnicity, admission FIM ratings, additional comorbidities (none, 1-3, and >3), type of stroke, and length of stay. RESULTS: We studied 47,853 patients with stroke, 368 with RA, and 119 with SLE. Discharge dispositions were similar for patients with RA and non-RA/SLE (81% discharged home). At discharge, the average FIM rating for patients with RA was 85.8, compared with 87.8 for non-RA/SLE patients. At followup, the average FIM rating for patients with RA was 95.9, compared with 99.6 for non-RA/SLE patients. RA was associated with lower FIM ratings at discharge and followup in multivariate analyses. SLE was associated with younger age (17.5 years). However, patients with SLE had similar discharge dispositions and FIM ratings to non-RA/SLE patients. CONCLUSION: RA was associated with lower functional status ratings at discharge and followup. Outpatient therapy for patients with RA may reduce long-term assistance. Patients with SLE were younger, but had similar functional outcomes to patients without RA/SLE, suggesting early morbidity from stroke among patients with SLE

18. NGUYEN TT, BEZOUSKA K, VAVRINCOVA P, SEDLACEK Pet HROMADNIKOVA I: Humoral response against Mycobacterium bovis Hsp65 derived fragments in children and young people with various disorders, J.Immunoassay Immunochem., Vol. 29(3), 281-298., 2008
    Organism:Department of Molecular Biology and Cell Pathology, Charles University in Prague, Prague, Czech Republic hiennguyen@lf3cuniczFAU - Nguyen, Thi Thu Hien
    Abstract:Using Western blotting, we investigated IgG antibodies against Mycobacterium bovis heat shock protein 65 (MB-Hsp65) fragments produced by cleavage with cyanogen bromide (CNBr) in 10 healthy controls, 11 patients with juvenile idiopathic arthritis (JIA), and 10 children with various diseases before haematopoietic stem cell transplantation (HSCT). CNBr cleaved MB-Hsp65 to three larger fragments: P1-163, P191-285, and P290-534. Sera of JIA patients and those before HSCT reacted with individual MB-Hsp65 fragments P1-163 and P290-534 significantly more frequently when compared with healthy controls. These results suggested that the key B-cell epitopes of MB-Hsp65 might be located on the aforementioned sequences

19. PRAHALAD S, BOHNSACK JF, WHITING A, CLIFFORD B, JORDE LB, GUTHERY SL, THOMPSON SD, GLASS DNet BAMSHAD MJ: Lack of association of functional CTLA4 polymorphisms with juvenile idiopathic arthritis, Arthritis Rheum., Vol. 58(7), 2147-2152., 2008
    Organism:Division of Immunology and Rheumatology, Department of Pediatrics, University of Utah School of Medicine, Salt Lake City, UT 84158-1289, USA prahal@geneticsutaheduFAU - Prahalad, Sampath
    Abstract:OBJECTIVE: Juvenile idiopathic arthritis (JIA) is an autoimmune disorder mediated by Th1 immune responses. CTLA-4, expressed on the T cell surface, plays a negative role in regulating T cell activation. Single-nucleotide polymorphisms (SNPs) in CTLA4 have been implicated in susceptibility to several autoimmune disorders, including JIA. This study was undertaken to test 3 functional CTLA4 variants for association with JIA. METHODS: Families of 531 children with JIA were genotyped for SNPs located in the promoter region (C-318T), exon 1 (A49G), and the 3'-untranslated region (CT60) of CTLA4 by polymerase chain reaction amplification and digestion. Family Based Association Testing (FBAT) was used to test CTLA4 SNPs and haplotypes for association with JIA. A second independent cohort of >300 children with JIA and >500 controls were genotyped for case-control analyses. Case-control analyses of the combined cohorts, as well as meta-analyses of published association studies of CTLA4 and JIA, were performed. RESULTS: There were no deviations of transmission of any of the CTLA4 variants to children with JIA, or JIA subtypes, determined by FBAT. No significant associations between CTLA4 C-318T or A49G SNPs and JIA were found in 650 JIA cases and 350 controls. Similarly, no significant associations with CT60 variants were found in >800 JIA cases and >500 controls. The meta-analysis also failed to confirm an association between JIA and CTLA4 variants. CONCLUSION: These results suggest that C-318T, A49G, CT60, and haplotypes tagged by these CTLA4 SNPs are not associated with JIA or major JIA subtypes

20. PRELOG M, SCHWARZENBRUNNER N, SAILER-HOCK M, KERN H, KLEIN-FRANKE A, AUSSERLECHNER MJ, KOPPELSTAETTER C, BRUNNER A, DUFTNER C, DEJACO C, STRASAK AM, MULLER T, ZIMMERHACKL LBet BRUNNER J: Premature aging of the immune system in children with juvenile idiopathic arthritis, Arthritis Rheum., Vol. 58(7), 2153-2162., 2008
    Organism:Department of Pediatrics, Medical University Innsbruck, Innsbruck, Austria MartinaPrelog@i-medacatFAU - Prelog, Martina
    Abstract:OBJECTIVE: Juvenile idiopathic arthritis (JIA) is an autoimmune disease of the young. The pathogenesis is not completely understood. Premature aging, associated thymic involution, and compensatory autoproliferation could play important roles in the pathogenesis of autoimmunity. We undertook this study to determine whether patients with JIA demonstrate premature immunosenescence. METHODS: To test this hypothesis, we measured 3 indicators of aging: the percentages and total counts of peripheral blood naive T cells, the frequency of T cell receptor excision circles (TRECs) in naive T cells, and telomeric erosion and Ki-67 expression as estimates of the replicative history of homeostatic proliferation. RESULTS: JIA patients showed an accelerated loss of CD4+,CD45RA+,CD62L+ naive T cells with advancing age and a compensatory increase in the number of CD4+,CD45RO+ memory T cells. JIA patients demonstrated a significantly decreased frequency of TRECs in CD4+,CD45RA+ naive T cells compared with age-matched healthy donors (P = 0.002). TREC numbers correlated with age only in healthy donors (P = 0.0001). Telomeric erosion in CD4+,CD45RA+ naive T cells was increased in JIA patients (P = 0.01). The percentages of Ki-67-positive CD4+,CD45RA+ naive T cells were increased in JIA patients (P = 0.001) and correlated with disease duration (P = 0.003), which was also an independent factor contributing to telomeric erosion (P = 0.04). CONCLUSION: Our findings suggest that age-inappropriate T cell senescence and disturbed T cell homeostasis may contribute to the development of JIA. In patients with JIA, dysfunction in the ability to reconstitute the T cell compartment should be considered when exploring new therapeutic strategies

21. QUARTIER P: [Still's disease (Systemic-Onset Juvenile Idiopathic Arthritis)], Arch.Pediatr., Vol. 15(5), 865-866., 2008
    Organism:Centre de reference national desmaladies rares Arthrites Juveniles, AP-HP, Unite d'Immuno-Hematologie et Rhumatologie Pediatrique, Hopital Necker-Enfants Malades, 149 rue de Sevres, 75015 Paris, France quartier@neckerfr <quartier@neckerfr>FAU - Quartier, P
    Abstract:

22. REININGA JK, LOS LI, WULFFRAAT NMet ARMBRUST W: The evaluation of uveitis in juvenile idiopathic arthritis (JIA) patients: are current ophthalmologic screening guidelines adequate?, Clin.Exp.Rheumatol., Vol. 26(2), 367-372., 2008
    Organism:Department of Ophthalmology, University Medical Centre Groningen (UMCG), University of Groningen, The NetherlandsFAU - Reininga, J K
    Abstract:OBJECTIVE: The aims of this study are to examine in our juvenile idiopathic arthritis (JIA) population: 1) the prevalence and characteristics of uveitis, 2) the complications and outcome of uveitis, 3) prognostic factors, and 4) the adequacy of the current ophthalmologic screening guidelines. METHODS: Retrospective analysis of medical records. RESULTS: 1) Of the 153 JIA patients included, 27 developed asymptomatic anterior uveitis (17.6%) - 7 unilateral and 20 bilateral. The 27 uveitis patients were significantly younger at JIA presentation than the 126 JIA patients without uveitis. 2) The following uveitis complications were noticed: glaucoma, cataract, posterior synechiae, cystoid macular oedema and papillitis. A visual outcome was acquired in 25 patients - 21 patients had a known visual acuity of > or = 0.1. Four patients had a visual acuity of <0.05 - 3 unilateral and 1 bilateral. 3) Female gender could not be confirmed as an independent risk factor for uveitis, neither was Anti Nuclear Antibody (ANA) positivity. We did not find a significant relationship between the moment of clinical remission of arthritis and of uveitis. 4) When applying current uveitis screening guidelines to our JIA population, we found that the optimum screening regimen would consist of a combination of the higher screening frequency of Southwood (1) and the longer screening period of the American Academy of Pediatrics (2) (AAP) screening guidelines. CONCLUSIONS: Uveitis is often encountered in JIA patients. It is a serious cause of morbidity. The use of disease-modifying antirheumatic drugs (DMARDs) probably has a positive effect on the preservation of visual function. We recommend a uveitis screening regimen which combines the AAP and Southwood guidelines and which includes rheumatoid factor positivity (RF+) and systemic onset patients in the quarterly screening

23. ROUSTER-STEVENS K, NAGESWARAN S, ARCURY TAet KEMPER KJ: How do parents of children with juvenile idiopathic arthritis (JIA) perceive their therapies?, BMC.Complement Altern.Med., Vol. 8, 25, 2008
    Organism:Department of Pediatrics, Wake Forest University School of Medicine, Winston-Salem, NC, USA krouster@wfubmceduFAU - Rouster-Stevens, Kelly
    Abstract:BACKGROUND: Complementary and alternative medical (CAM) therapies are commonly used by pediatric patients with chronic medical conditions. Little is known about parents' perceptions of these therapies. This study describes the views of parents of patients with juvenile idiopathic arthritis (JIA) regarding conventional and CAM therapies. METHODS: Parents of children with JIA seen at a pediatric rheumatology clinic were surveyed between June 1 and July 31, 2007. Questionnaires asked about patients' use of over 75 therapies in the past 30 days, their perceived helpfulness (0 = not helpful; 3 = very helpful), perceived side effects (0 = none; 3 = severe), and whether each therapy would be recommended to other patients with JIA (Yes, No, Not sure). RESULTS: Questionnaires were returned by 52/76 (68%) parents; patients' average age was 10.9 years and 87% were Caucasian. Medications were used by 45 (88%) patients; heat (67%) and extra rest (54%) were also commonly used. CAM therapies were used by 48 (92%), e.g., massage (54%), vitamins and other supplements (54%), avoiding foods that worsened pain (35%) and stress management techniques (33%). Among the therapies rated by 3 or more parents, those that scored 2.5 or higher on helpfulness were: biologic medications, methotrexate, naproxen, wheelchairs, orthotics, heat, vitamins C and D, music, support groups and prayer. CAM therapies had 0 median side effects and parents would recommend many of them to other families. CONCLUSION: JIA patients use diverse therapies. Parents report that many CAM therapies are helpful and would recommend them to other parents. These data can be used in counseling patients and guiding future research

24. SALAVOURA K, DRACOU C, KOLIALEXI A, DRAKONAKI S, SOFOCLEOUS Cet MAVROU A: Juvenile idiopathic arthritis-type disease associated with chromosomal aberrations, Clin.Exp.Rheumatol., Vol. 26(2), 347-350., 2008
    Organism:Department of Medical Genetics, Athens University School of Medicine, Athens, Greece akolial@ccuoagrFAU - Salavoura, K
    Abstract:The association of certain chromosome aberrations with arthropathy has been previously described, but there is a limited number of reports in the literature. Two children are described, one with 18q- syndrome and another with supernumary marker chromosome 15, both presenting with juvenile idiopathic arthritis-type disease, aggressive progression and moderate response to inflammatory, corticosteroid and immunosuppressive treatment

25. SIROIS FM: Provider-based complementary and alternative medicine use among three chronic illness groups: associations with psychosocial factors and concurrent use of conventional health-care services, Complement Ther.Med., Vol. 16(2), 73-80., 2008
    Organism:Department of Psychology, University of Windsor, 401 Sunset Ave, Windsor, Ontario, Canada N9B 3P4 fsirois@uwindsorcaFAU - Sirois, Fuschia M
    Abstract:OBJECTIVE: The focus of this study was to examine the patterns of provider-based complementary and alternative medicine (CAM) use across three chronic illness groups, and to identify the socio-demographic, health-related, and psychosocial factors associated with CAM use. DESIGN: Cross-sectional international survey administered on the Internet to individuals with arthritis, inflammatory bowel disease (IBD), and mixed chronic conditions. MAIN OUTCOME MEASURES: Self-reported consultations to CAM providers and to a variety of conventional health-care services made in the previous 6 months. RESULTS: 365 surveys were received from people with arthritis (N=140), IBD (N=110), and other chronic conditions (N=115). Overall 38.1% of respondents had used CAM, with rates ranging from 31.8 to 46.1% across the three illness groups. Backward step-wise logistic regression revealed that being female, having more than high school education, a greater number of comorbid conditions, higher perceived control over health and reward motivations, lower stress and less belief that health is governed by chance, were the best predictors of CAM consultations. CAM clients also used a greater variety of conventional health-care services and made more consultations relative to non-CAM clients. CONCLUSIONS: In this study the socio-demographic and health status factors associated with CAM consultations in three different chronic illness groups were similar to those found in the general population. CAM use in the study population was also related to higher use and a greater variety of use of conventional health-care services, and with stronger beliefs in the controllability of health and an enduring motivation to seek out rewards

26. SKYTTA ET, SAVOLAINEN A, KAUTIAINEN HJet BELT EA: Outcome after temporary physeal stapling for knee valgus deformity in children with JIA, Arch.Orthop.Trauma Surg., 2008
    Organism:Paijat-Hame Central Hospital, Keskussairaalankatu 7, 15850, Lahti, Finland, eerikskytta@fimnetfi
    Abstract:INTRODUCTION: Majority of children with secondary knee valgus deformity due to juvenile idiopathic arthritis (JIA) are affected by the polyarthritic disease subtype. Progressive rheumatoid knee destruction in patients with JIA and valgus deformity may necessitate total knee replacement (TKR) at a young age. Temporary physeal arrest is a safe and effective method for correction of knee valgus malalignment prior to closure of the epiphyseal growth plates even during active arthritis. RESULTS: Most of the angular correction achieved in the stapled knees (n = 103) in the present cohort remained the same through the long-term follow-up though in some patients the deformity did recur. The advantages of angular correction prior to possible future TKR include easier soft tissue balancing, diminished bony deformity and less deranged collateral ligaments reducing the need for expensive custom and constrained implants. CONCLUSION: However, the effect of the correction on postponing the early need for TKR is limited

27. SYED RH, GILLIAM BEet MOORE TL: Prevalence and significance of isotypes of anti-cyclic citrullinated peptide antibodies in juvenile idiopathic arthritis, Ann.Rheum.Dis., Vol. 67(7), 1049-1051., 2008
    Organism:

28. TAPPEINER C, ROESEL M, HEINZ C, MICHELS H, GANSER Get HEILIGENHAUS A: Limited value of cyclosporine A for the treatment of patients with uveitis associated with juvenile idiopathic arthritis, Eye., 2008
    Organism:1Department of Ophthalmology, Uveitis Center, St Franziskus Hospital, Muenster, Germany
    Abstract:AimsJuvenile idiopathic arthritis (JIA) is often associated with severe chronic anterior uveitis (CAU), and immunosuppressive therapy may be required. In this study, the value of cyclosporine A (CsA) as monotherapy or as combination therapy for treating uveitis was studied in a large cohort of JIA children.MethodsMulticentre retrospective study including 82 JIA children (girls n=60) suffering from unilateral or bilateral (n=55) CAU. The indication for CsA was active uveitis, although patients were on topical or systemic corticosteroids, MTX, or other immunosuppressive drugs.ResultsInactivity of uveitis during the entire treatment period (mean 3.9 years) was obtained with CsA monotherapy in 6 of 25 (24%) patients, but more often when CsA was combined with the immunosuppressives (35/72 patients; 48.6%, P=0.037), or MTX (18/37 patients, 48.6%, P=0.065), which had already been given. With CsA (mean dosage 2.9 mg/kg), systemic immunosuppressive drugs and steroids could be reduced by >/=50% (n=19) or topical steroids reduced to </=2 drops/eye/day (n=40) in selected patients. Pre-existing cystoid macular oedema did not resolve under CsA treatment in any of the patients. In nine patients (11%), CsA was discontinued because of systemic hypertension (n=1), elevated creatinine levels (n=3), or other adverse effects (n=5).ConclusionsThese observations suggest that CsA has limited value as a second-line immunosuppressive drug for the treatment of JIA-associated CAU. The efficacy was better as the combination therapy in patients not responding to other immunosuppressives (eg, MTX) than the systemic monotherapy.Eye advance online publication, 13 June 2008; doi:10.1038/eye.2008.174

29. VAN SUMMEREN MJ, VERMEER C, ENGELBERT RH, SCHURGERS LJ, TAKKEN T, FISCHER Ket KUIS W: Extremes in vitamin K status of bone are related to bone ultrasound properties in children with juvenile idiopathic arthritis, Clin.Exp.Rheumatol., Vol. 26(3), 484-491., 2008
    Organism:Department of Paediatric Immunology, University Medical Centre Utrecht, The Netherlands mjhvansummeren@umcutrechtnlFAU - van Summeren, M J H
    Abstract:OBJECTIVE: Osteopenia is a common complication of juvenile idiopathic arthritis (JIA). In adults, low bone density and increased fracture risk are associated with low vitamin K status of bone. The vitamin K-dependent protein osteocalcin plays an important role in bone metabolism. Its activity depends upon post-translational carboxylation in which vitamin K is an essential co-factor. Hence, vitamin K deficiency leads to under-carboxylated (i.e., inactive) osteocalcin (ucOC). Little is known about the vitamin K status and bone health in children with juvenile idiopathic arthritis (JIA). We studied the vitamin K status of bone and its association with bone mass properties in children with JIA compared to healthy children. METHODS: We performed a cross sectional study in 55 children with JIA and 54 healthy controls between 6-18 years of age. Bone markers, ultrasound bone mass properties and vitamin K status of bone were determined. RESULTS: Overall, no differences in vitamin K status of bone were found between the study groups. Among children with JIA, a high ratio of ucOC/cOC indicating low vitamin K status was associated with low bone ultrasound parameters, whereas children with a high vitamin K status had markedly higher bone properties. This association was independent of physical activity, age, gender and BMI. CONCLUSION: These results suggest that vitamin K may be one of multiple risk factors for low bone mass in children with JIA, in addition to other recognized determinants of bone mass. The question remains whether JIA patients would benefit from increased dietary vitamin K intake

30. WONG AR, NOOR AS, RASOOL AH, QUAH BSet ROBERTON D: Pulmonary haemosiderosis with juvenile idiopathic arthritis in a Malaysian child, Med.J.Malaysia., Vol. 62(4), 352-354., 2007
    Organism:Department of Paediatrics, School of Medical Sciences, Universiti Sains Malaysia, KelantanFAU - Wong, A R
    Abstract:A rare case of childhood pulmonary haemosiderosis with juvenile idiopathic arthritis is discussed, with particular reference to treatment with hydroxychloroquine and sildenafil for pulmonary hypertension which occurs secondary to this disease

31. ZAUTRA AJ, DAVIS MC, REICH JW, NICASSARIO P, TENNEN H, FINAN P, KRATZ A, PARRISH Bet IRWIN MR: Comparison of cognitive behavioral and mindfulness meditation interventions on adaptation to rheumatoid arthritis for patients with and without history of recurrent depression, J.Consult Clin.Psychol., Vol. 76(3), 408-421., 2008
    Organism:Department of Psychology, Arizona State University, Tempe, AZ 85287-1104, USA alexzautra@asueduFAU - Zautra, Alex J
    Abstract:This research examined whether cognitive behavioral therapy and mindfulness interventions that target responses to chronic stress, pain, and depression reduce pain and improve the quality of everyday life for adults with rheumatoid arthritis (RA). The 144 RA participants were clustered into groups of 6-10 participants and randomly assigned to 1 of 3 treatments: cognitive behavioral therapy for pain (P); mindfulness meditation and emotion regulation therapy (M); or education-only group (E), which served as an attention placebo control. The authors took a multimethod approach, employing daily diaries and laboratory assessment of pain and mitogen-stimulated levels of interleukin-6 (IL-6), a proinflammatory cytokine. Participants receiving P showed the greatest Pre to Post improvement in self-reported pain control and reductions in the IL-6; both P and M groups showed more improvement in coping efficacy than did the E group. The relative value of the treatments varied as a function of depression history. RA patients with recurrent depression benefited most from M across several measures, including negative and positive affect and physicians' ratings of joint tenderness, indicating that the emotion regulation aspects of that treatment were most beneficial to those with chronic depressive features

32. ZHOU P, TEN S, SINHA S, RAMCHANDANI N, VOGIATZI Met MACLAREN N: Insulin receptor autoimmunity and insulin resistance, J.Pediatr.Endocrinol.Metab., Vol. 21(4), 369-375., 2008
    Organism:Division of Pediatric Endocrinology, Albert Einstein College of Medicine, Bronx, NY 10467, USA pzhou@montefioreorgFAU - Zhou, Ping
    Abstract:The frequency of insulin receptor autoantibodies (IR-ab) was determined among adolescents and young adults with documented insulin resistance syndrome (IRS) with and without concomitant autoimmunity. The study population was comprised of 61 patients with obesity, acanthosis nigricans and insulin resistance (simple IRS); 12 with IRS and other autoimmune problems (lupus erythematosus, rheumatoid arthritis, dermatomyositis) (type B insulin resistance); six with autoimmune polyglandular syndrome type 2; and 40 healthy controls. Using our newly developed radiobinding assay system, we found no control positive while 25% of the patients with type B IRS (3/12) were positive, as expected. However, we found that 9.8% of the patients with simple IRS (6/61) were also reproducibly positive. All the latter patients with positive IR-ab were female with ovarian hyperandrogenism. The phenotype of those affected was otherwise unremarkably different from those without IR-ab. Our findings suggest that autoimmunity to insulin receptors may be causal in IRS especially for females with ovarian hyperandrogenism, and that IR-ab may be found in IRS besides those previously defined by the type B phenotype. Determining the level of IR-ab in childhood onset IRS may provide mechanistic insights into the genesis of insulin resistance and lead to novel treatment approaches