Drug survival and reasons for discontinuation of the first course of biological therapy in 301 juvenile idiopathic arthritis patients.

The objective of this study was to determine long-term effectiveness and safety of 1st biological treatment (BT) in a cohort of 301 juvenile idiopathic arthritis (JIA) patients (pts), non-responders to disease-modifying antirheumatic drugs (DMARDs), in terms of drug survival (continuation rate on therapy) and to identify the baseline predictors of treatment discontinuation. Each JIA pt enrolled in BT is prospectively assessed at the start of treatment and then every 2 months for the evaluation of safety and efficacy according to ACR-Pedi30 criteria. All clinical charts of pts who started a BT between November 1999 and July 2010 have been reviewed. Survival analysis methods suitable for competing risks were used to study time to drug discontinuation due to disease control (defined according to Wallace criteria) or failure [adverse event (AE), lack of efficacy (LaE) or loss of efficacy (LoE) according ACR-Pedi30]. A number of 301 JIA pts, non-responders or intolerant to DMARDs and treated with one or more cycles of BT, were identified. Median disease duration, from onset to the beginning of 1st BT, was 7.8 years (interquartil range 2.21-15.1). In total, there were 294 1st corses with anti-TNF agents, 5 with abatacept and 2 with anakinra. A number of 298 pts were included in the analysis for drug discontinuation (3 pts with no follow-up data after their first dose of BT were excluded). The median follow-up on treatment, before discontinuation due to every cause, was 53.7 months (range 0.45-124.45). One hundred and sixty-five pts discontinued BT: 27 due to disease control, 135 because of failure (78 AEs, 12 LaE and 45 LoE), 3 pts temporarily stopped for pregnancy. Among 135 pts who discontinued for failure, 117 switched to a 2nd BT. Among 27 pts who discontinued due to remission, 13 pts restarted on BT for relapse of disease activity (10 pts restarted with the same BT, 3 switched to a different one). Predictors of discontinuation due to AE were female gender (P=0.01) and longer disease duration (P=0.02). Predictors of discontinuation due to LaE or LoE were systemic onset and polyarthritis FR positive (vs other JIA subtypes) (P<0.05) and use of mAb-anti-TNF (vs sTNFR) (P=0.02). Predictors of discontinuation due to inactive disease were male gender and shorter disease duration (P<0.05). Although only few pts discontinued BT due to a complete and persistent disease control, the majority of them remained on BT for a long time, suggesting that in our cohort of JIA pts, affected by a severe long lasting refractory disease, BT was globally well tolerate and efficacious in controlling the disease.

Primary Sjögren syndrome: report of a 10 years old girl with local edema and positivity of anti SS-A and anti SS-B autoantibodies.

Sjogren-Larsson syndrome (SLS) is an autoimmune disease, uncommon in childhood. We report a case of SLS in a 10-year-old girl with a history of tumor, calor and rubor in the back of her toes almost every month, which resolved in 4-5 days without therapy. She did not complain of dry mouth or dry eyes. The laboratory findings showed high inflammation markers, rheumatoid factor 128 IU, Waaler-Rose 256 IU, anti nuclear antibody (ANA) 1/640, SSA (anti Sjogren antigen A) and SSB (anti Sjogren antigen B) positive and hypergammaglobulinemia. The Schirmer's test resulted to be pathologic, the ultrasonography images and biopsy of minor salivary glands revealed focal periductal lymphocytic infiltrate and sialoduct ectasia class IV of juvenile Sjogren syndrome. The juvenile Sjogren syndrome is frequently under-diagnosed. Clinical manifestations in children might be different from the adult form, although laboratory findings may be similar to those found in adults.

Focus on adverse events of tumour necrosis factor alpha blockade in juvenile idiopathic arthritis in an open monocentric long-term prospective study of 163 patients.

OBJECTIVE: To report adverse events (AEs) seen in a large cohort of patients with juvenile idiopathic arthritis (JIA) treated with tumour necrosis factor (TNF)alpha blockers (infliximab and etanercept). METHODS: All patients with JIA treated with infliximab or etanercept at the Paediatric Rheumatologic Centre of the G Pini Institute (Milan, Italy) from November 1999 to February 2006, were enrolled in an open, single-centre, long-term prospective study RESULTS: In all, 163 patients (68 infliximab, 95 etanercept) were enrolled. Mean (SD) age of onset was 6.4 (4.8) years, mean age 17.1 (9.2) years, mean therapy duration 22.9 (17.6) months. A total of 45 patients (32 infliximab, 13 etanercept) failed to respond to or did not tolerate the first therapy and switched to a second one. In all, 208 treatments (81 infliximab, 127 etanercept) were performed. A total of 71 AEs occurred in 51 (62.9%) patients on infliximab and led to discontinuation in 26 (32.1%); 133 AEs occurred in 69 (54.3%) patients on etanercept and led to discontinuation in 18 (14.2%). Some AEs, such as thrombocytopoenia, neuropsychiatric disorders, new onset of Crohn disease and new onset or flare-up of chronic iridocyclitis (CIC), are unusual and have rarely been described before, yet proved to be significant in frequency and/or clinically noteworthy in the large population we followed. CONCLUSIONS: In our 6-year study, anti-TNFalpha agents infliximab and etanercept were well tolerated and safe, and were associated with only few serious, but all reversible, AEs. However, such inhibitors are associated with various and numerous AEs. Children and young adults affected by JIA should be carefully monitored so as to limit the risk of AEs during anti-TNFalpha therapy as much as possible.

Methotrexate improves the health-related quality of life of children with juvenile idiopathic arthritis.

OBJECTIVES: To examine the change in health-related quality of life (HRQOL) and its determinants in children with juvenile idiopathic arthritis (JIA) treated with methotrexate (MTX). METHODS: Patients were extracted from the PRINTO clinical trial which aimed to evaluate the efficacy and safety profile of MTX administered in standard, intermediate or higher doses (10, 15 and 30 mg/m(2)/week respectively). Children with polyarticular-course JIA, who were less than 18 years and had a complete HRQOL assessment were included. RESULTS: A total of 521 children were included. At baseline, patients with JIA showed poorer HRQOL (p<0.01) than healthy children. In 207/412 (50%) and 63 (15%) children, HRQOL values were 2 standard deviations below the mean of healthy controls in the physical and psychosocial summary scale, respectively. After 6 months of treatment with standard dose MTX, there was a statistically significant improvement in all HRQOL health concepts, particularly the physical ones. Similar improvements were observed in those who did not respond to a standard dose of MTX and were subsequently randomised to a higher dose. The presence of marked disability at baseline was associated with a fivefold increased risk of retaining poor physical health after 6 months of active treatment with standard dose MTX. Other less important determinants of retaining poor physical well-being were the baseline level of systemic inflammation, pain intensity and an antinuclear-antibody-negative status. CONCLUSIONS: MTX treatment produces a significant improvement across a wide range of HRQOL components, particularly in the physical domains, in patients with JIA.

Preliminary evidence that etanercept may reduce radiographic progression in juvenile idiopathic arthritis.

OBJECTIVE: To investigate the rate of radiographic progression, as measured with the carpo-metacarpal ratio (Poznanski score), during etanercept (ETN) therapy in children with polyarticular juvenile idiopathic arthritis (JIA). METHODS: Patients included in the Italian ETN registry who had a standard radiograph of both hands and wrists in the posteroanterior view made at start of treatment and after 1 year were included in the study. The clinical response was assessed by means of the ACR Pediatric definition of improvement. Radiographic progression was determined by calculating the change in the Poznanski score between the baseline and the 1-year radiographs. RESULTS: A total of 40 patients were studied. The frequency of ACR pediatric 30, 50, and 70 response at 1 year was 77%, 72%, and 50%, respectively. The median change in the Poznanski score between baseline and 1 year was + 0.3 units, meaning that, on average, patients experienced improvement in radiographic progression. CONCLUSION: Our pilot study provides evidence that ETN is potentially capable of reducing the progression of radiographic joint damage in JIA. This finding deserves confirmation in a controlled trial.

[Skeletal mineralization in a prepubertal female population affected by juvenile idiopathic arthritis]. / Mineralizzazione scheletrica in una popolazione femminile prepubere affetta da artrite idiopatica giovanile.

BACKGROUND: Puberty is an essential step in bone mass accrual. Growth failure and impairment of sexual maturation are frequent manifestations of chronic illnesses in the paediatric population, and chronic rheumatologic disorders such as juvenile idiopathic arthritis (JIA) are no exception to this. METHODS: The aim of our study was to prospectively evaluate bone density in adolescent females with JIA, and to correlate the results with clinical variables, in particular with age at menarche. Lumbar spine (L2-L4) area bone mineral density (aBMD) (assessed by Dual X-ray Absorbiometry, DXA) was monitored every 6-12 months in a group of 38 girls with JIA. The evaluated bone density accrual during the peripubertal time as well as absolute and relative (Z-score) aBMD in relationship with age at menarche, JIA subset, disease activity (as evaluated by ESR and Hgb), corticosteroid and methotrexate treatment (mean pro kg daily dose, cumulative dose) was assessed. Height, body mass index (BMI), bone mass content (BMC) values were also collected. Volumetric BMD (vBMD) evaluated with a geometric correction formula has been calculated and compared to aBMD. RESULTS: Patients were divided into two groups: - group I included girls with menarche age within normal limits for Italian standards; - group II included girls with delayed menarche. The BMD values and Z scores in group I were not significantly different to normal population. The BMD values and Z scores in group II were significantly decreased when compared to the normal population (p<0.001). With a multivariate analysis only age at menarche seemed independently related to peripubertal mineralization (p=0.025, r between -0.65 and -0.75). With a binary logistic analysis only disease activity (ESR and Hgb values) seems independently related to a menarche delay (1.24+/-0.4 for each mm/h). CONCLUSION: Our data show a critical role for disease activity in determination of a regular pubertal onset and an optimal bone density achievement.

[Biological therapy with TNF-inhibitors in pediatric rheumatology. Review of the literature and personal experience]. / Le terapie biologiche con inibitori del TNF in reumatologia pediatrica. Revisione della letteratura ed esperienza personale.

The therapeutic approach to JIA is sometimes very troublesome and progression to erosive polyarthritis may occur in all JIA categories. Only Methotrexate has shown efficacy and safety in a large controlled trial. Nevertheless, in many cases, drug resistance or intolerance has led to try other therapeutic options, with still debatable results. Therefore, there has been space, in the last few years, for new therapies as the TNF-inhibitors. This therapeutic approach has shown a dramatic clinical benefit in active polyarticular refractory JIA: the rate and rapidity of response have exceeded those of all other studied DMARDs. Preliminary data show that they are efficacious also for other pediatric rheumatic disease (spondyloarthropathies, autoimmune uveitis, dermatomyositis, Kawasaki syndrome and some autoinflammatory diseases). TNF-inhibitors in JIA have demonstrated a favourable benefit-to-risk profile. However, as their use has increased worldwide, some unusual, usually not serious, adverse events have emerged. Severe infections, including TB, and deaths have been reported. Long-lasting active disease, systemic disease, concurrent and previous immunosuppressive therapies, all contribute to risk of infection and other serious AEs. Given the evidence that TNF has a primary role in the pathogenesis of JIA, particularly in joint destruction, neutralizing this cytokine early, within the window of opportunity, could halt or delay progression of joint damage and debilitating consequences of the disease. Thus, for JIA patients whose disease is not quickly controlled with MTX, TNF blockers may be considered as first-line treatment, although long-term safety data still need to be established.

[Italian Society of Rheumatology (SIR) recommendations for performing arthrocentesis]. / Raccomandazioni della Società Italiana di Reumatologia per l'esecuzione dell'artrocentesi.

Joint fluid aspiration, or arthrocentesis, is one of the most useful and commonly performed procedures for the diagnosis and treatment of rheumatic diseases, but to date no definite guidelines have been published. For this reason, a group of experts of the Italian Society of Rheumatology (SIR) produced evidence based recommendations for performing arthrocentesis. Among them, the most relevant are: a) arthrocentesis is necessary when synovial effusion of unknown origin is present, especially if septic or crystal arthritis is suspected; b) the patient should be clearly informed of the benefits and risks of the procedure in order to give an informed consent; c) ultrasonography should be used to facilitate arthrocentesis in difficult joints; d) fluid evacuation often has a therapeutic effect and facilitates the success of the following intraarticular injection; e) careful skin disinfection and the use of sterile, disposable material is mandatory for avoiding septic complications. Disposable, non sterile gloves should always be used by the operator, mainly for his own protection; f) contraindications are the presence of skin lesions or infections in the area of the puncture; g) the patient's anticoagulant treatment is not a contraindication, providing the therapeutic range is not exceeded; h) joint rest after arthrocentesis is not indicated. Several of these recommendations were based on experts' opinion rather than on published evidence which is scanty.

[Long-term evaluation of infliximab in the treatment of persistently active juvenile idiopathic arthritis refractory to conventional therapy]. / Valutazione a lungo termine di infliximab nel trattamento dell'artrite idiopatica giovanile persistentemente attiva e refrattaria alle terapie convenzionali.

OBJECTIVES: To evaluate, in long-term open label prospective study, infliximab as therapeutic choice for Juvenile Idiopathic Arthritis (JIA) non responsive to conventional therapy. METHODS: We enrolled to treat with infliximab 78 JIA patients (66 females, 12 males): the mean age was 20.7+/-7.1 years (median 20.9, range 5.4-34.9); mean JIA duration was 13.6+/-7.6 years (median 13.5, range 0.4-31.4). Infliximab, at dose of 3-10 mg/kg/infusion added to weekly subcutaneous Methotrexate or other previous DMARDs, was administered by intravenous infusions at weeks 0, 2, 6 and every 8 weeks thereafter. Chest X-ray, Mantoux's test, electrocardiogram were performed at baseline; laboratory tests and clinical evaluation were performed at each infusion. Response was evaluated according to ACR improvement criteria. RESULTS: Mean treatment period was 21.6 months+/-18.8 (median 14.7, range 1.4-72.4). Just after first infusion most of patients reported significant improvement in pain, fatigue, morning stiffness. Infliximab is still successfully administered to 23 patients (29.5%); 55 (70.5%) patients suspended because of: inefficacy (7), infusion reactions (17), adverse events (9), disease flare-up after a period of effectiveness on synovitis, pain, and morning stiffness (19), remission (2), lack of compliance to treatment (1). Infusion reactions, like dyspnea, flushing, chills, headache, hypotension, anxiety, throat oedema, were observed in 29 patients (34.5%). Anti-DNA antibodies were present in 7 patients (none developed Systemic Lupus Erythematous). CONCLUSIONS: Infliximab showed impressive effectiveness treating refractory JIA, although most of patients had to discontinue treatment because of disease flare-up or adverse events. Infliximab may represent a good therapeutic choice in patients non-responders to Methotrexate.

Cyclosporine A in juvenile idiopathic arthritis. Results of the PRCSG/PRINTO phase IV post marketing surveillance study.

OBJECTIVE: To investigate the clinical use patterns, clinical effect and safety of cyclosporine A (CSA) in juvenile idiopathic arthritis (JIA) in the setting of routine clinical care. METHODS: An open-ended, phase IV post marketing surveillance study was conducted among members of the Pediatric Rheumatology Collaborative Study Group (PRCSG) and of the Paediatric Rheumatology International Trials Organisation (PRINTO) to identify patients with polyarticular course JIA who had received CSA during the course of their disease. RESULTS: A total of 329 patients, half of whom had systemic JIA, were collected in 21 countries. Data were collected during 1240 routine clinic visits. CSA was started at a mean of 5.8 years after disease onset and was given at a mean dose of 3.4 mg/kg/day. The drug was administered in combination with MTX in 61% and along with prednisone in 65% of the patients who were still receiving CSA. Among patients who were still receiving CSA therapy at the last reported visit, remission was documented in 9% of the patients, whereas in 61% of the patients the disease activity was rated as moderate or severe. The most frequent reason for discontinuation of CSA was insufficient therapeutic effect (61% of the patients); only 10% of the patients stopped CSA because of remission. In 17% of the patients, side effects of therapy was given as the primary reason for discontinuation. CONCLUSION: This survey suggests that CSA may have a less favourable efficacy profile than MTX and etanercept, whereas the frequency of side effects may be similar. The exact place of CSA in the treatment of JIA can only be established via controlled clinical trial.

Capillaroscopic observations in childhood rheumatic diseases and healthy controls.

OBJECTIVE: To describe, by using video nailfold capillaroscopy (NFC), microvascular abnormalities in children with rheumatic diseases and to evaluate the capillary changes over a follow up period. METHODS: 118 children suffering from rheumatic diseases: 55 juvenile idiopathic arthritis (JIA), 7 mixed connective tissue disease (MCTD), 6 primary Raynaud's phenomenon (PRP), 34 systemic lupus erythematosus (SLE), 8 juvenile systemic sclerosis (JSSc) and 8 juvenile dermatomyositis (JDM) were included in the study. Patients with major capillaries abnormalities or scleroderma pattern were followed up for at least 12 months. 70 age- and sex-matched healthy controls (HC) were also examined. RESULTS: In HC there was a significant correlation between age and capillary length (p = 0.001). JIA patients showed capillary number, size, shape and arrangement similar to HC. Minor abnormalities were frequently observed. The percentage of major abnormalities were significantly increased compared to HC in MCTD (p = 0.008), SLE (p = 0.0002) and JDM patients (p < 0.0001). 5/8 of JSSc had a scleroderma pattern from the onset of the disease. The serial observations in connective tissue diseases also showed that the evolution of capillaroscopic pattern was not unidirectional. In fact, in some nailfolds there was an increase in capillary loss and in avascular areas, whereas sometimes it remained stable on repeated examination. CONCLUSION: NFC can be used as a simple, inexpensive, non-invasive method to evaluate the microvascular abnormalities in childhood rheumatic conditions, and it may be useful in early recognition and monitoring scleroderma spectrum disorders.

[Temporomandibular joint involvement in juvenile idiopathic arthritis: treatment with an orthodontic appliance]. / Trattamento con un dispositivo ortodontico per l'impegno temporomandibolare nell'artrite idiopatica giovanile. Osservazioni su 72 casi.

OBJECTIVE: About 65% of children suffering from juvenile idiopathic arthritis (JIA) shows a more or less marked involvement of temporo-mandibular joint (TMJ) with altered mandibular growth, resorption of the condyles, occlusary instability, reduced chewing ability and facial dysmorphia. The purpose of our study is to prevent and to treat the progressive evolution of JIA on craniofacial growth and morphology with a functional appliance; surgery should be considered only in so far as the adequacy of TMJ movement is concerned. METHODS: From 1992 until now 72 children with proved JIA and TMJ involvement have been treated (50 females, 22 males, aged 6 to 16 years old). TMJ involvement was bilateral in 61% and unilateral in 39% of patients. A diagnostic workup was carried out involving tomograms of TMJ and cephalometric radiograph and analysis. The authors used a bimaxillary activator in the attempt to modify the unfavourable growth pattern and provide a gradual ante-rotation of the jaw. RESULTS: Almost all JIA patients showed satisfactory long term results, easing of pain, reduced skeletal discrepancy, increased function and good facial profile. CONCLUSIONS: The long term results of this study indicate that orthopaedic therapy might control the vicious circle of the malocclusion in children with JIA, preventing exacerbation of mandibular clockwise rotation. Surgical intervention for the improvement of TMJ function should be considered only if a severe restricted state is imminent.

Evaluation by dual-photon absorptiometry of bone mineral loss in rheumatic children on long-term treatment with corticosteroids.

The introduction of reliable and non-invasive methods of measuring bone mass has allowed investigators to study the bone mass loss (ostopenia) related to rheumatic diseases and corticosteroid therapy. Serial measurements of lumbar bone mineral density (BMD) by dual-photon absorptiometry (DPA) is an effective method of checking bone mineralisation. In children, however, the bone mass is not constant over time, so bone densitometric measurements must take into account not only the net loss but also the missing increase in BMD. In order to study the effects of both chronic rheumatic disease and the long-term administration of corticosteroids in children, as a first step the reference curves of bone mineralisation (mean BMD values and annual % BMD growth rates) were calculated from a control population of 79 children (32 males and 47 females) aged 3 to 20 years. All the subjects involved in the study underwent DPA utilising a Norland Bonestar instrument provided with a 153 Gadolinium source and the average BMD (g/cm2) of the lumbar spine was calculated. As a second step, a transverse study was carried out on a series of 157 children and young adults affected by chronic rheumatic diseases with juvenile onset. As a third step, a longitudinal study on the adverse effect of the chronic administration of corticosteroids on bone mineralisation was carried out on a series of 58 patients affected by chronic rheumatic diseases with juvenile onset who were being treated with long-term corticosteroids. Serial measurements of bone mass should help us to improve our strategies in preventing and counteracting osteopenia due to the chronic administration of corticosteroids also in children.

Lung function and diffusing capacity for carbon monoxide in patients with juvenile chronic arthritis: effect of disease activity and low dose methotrexate therapy.

OBJECTIVE: We measured lung function, in terms of lung volumes, forced expiratory flow-volume curves and diffusing capacity of carbon monoxide (DLCO), in a group of 61 patients with juvenile chronic arthritis (42 female; age range 5 to 33 years) to ascertain whether disease activity and treatment with low dose methotrexate (MTX) influenced these parameters. The whole population was divided into subgroups based on onset type (systemic, n = 27; pauciarticular, n = 12; polyarticular, n = 22), disease activity (active, n = 42; inactive, n = 19), and MTX treatment (treated, n = 27; not treated, n = 34). RESULTS: We found that maximal-mid expiratory flow (MMEF) was significantly reduced in patients with active disease (p < 0.025). The mean DLCO value, expressed as a percentage of the predicted value, and DLCO corrected for the hemoglobin value were lower than expected (67% and 80%, respectively). Multiple regression analysis showed that the forced vital capacity (FVC), forced expiratory flow in one second (FEV1) and DLCO were all correlated to the clinical subtype of the disease (p < 0.05, p < 0.02, p < 0.02, respectively), and MMEF was related to disease activity (p < 0.025). There was no evidence of any effect of MTX treatment on the pulmonary parameters. CONCLUSION: This study confirms that JCA is characterized by an impairment of lung function, mainly involving the small airways, and by interstitial damage. These changes are related to the clinical subtypes of the disease and to disease activity.

Autoantibodies to chromatin: prevalence and clinical significance in juvenile rheumatoid arthritis.

OBJECTIVE: To determine the prevalence of anti-chromatin antibodies (Abs) in juvenile rheumatoid arthritis (JRA) and to assess any association between the presence of anti-chromatin Abs and clinical subsets of the disease. METHODS: IgG anti-chromatin Abs and anti-extractable nuclear antigens (ENA) Abs were detected by an enzyme-linked immunosorbent assay (ELISA), and antinuclear Abs (ANA) by indirect immunofluorescence in sera of 89 children with JRA. Ten children with systemic, 32 with polyarticular and 47 with pauciarticular disease onset (uveitis occurred in 17/47 children) were studied. As a control group, 12 sera of patients suffering from idiopathic uveitis and 31 age- and-sex-matched healthy children (HC) were examined. RESULTS: Abs to chromatin were detected in 14/47 (29.8%) of children suffering from pauciarticular onset JRA and in this group the higher prevalence of anti-chromatin Abs has been found in children with chronic uveitis (p = 0.002). Anti-chromatin positivity was observed in 2/10 (20%) of systemic and in 3/32 (9.3%) of polyarticular onset JRA. Furthermore, none of the patients with idiopathic uveitis and HC had Abs to chromatin. anti-chromatin Abs titers remained relatively stable over a 6-month control period. CONCLUSION: Our results confirm previous data about the presence of circulating anti-chromatin Abs in juvenile arthritis. Interestingly, anti-chromatin Abs were significantly higher in the group of patients with pauciarticular onset with past or present history of uveitis, than in patients without ocular involvement. A long-term follow-up study could be useful to demonstrate the potential utility of these autoantibodies in diagnosing, classifying and treating children affected.

Validation of the Italian version of the Stanford Childhood Health Assessment Questionnaire for measuring functional status in children with chronic arthritis.

The Stanford Health Assessment Questionnaire developed by Singh et al. to measure functional status in children with chronic arthritis (CHAQ) was translated into Italian (I-CHAQ), with minor modifications to obtain cross-cultural equivalence. This version was evaluated in a series of 96 patients with juvenile rheumatoid arthritis (JRA), both males and females ranging in age from 3 to 19 years (mean age 9.9 years). All three onset subtypes and all four classes of disability were represented in the sample. The questionnaire was filled in by the parents if the children were less than 8 years of age (23 cases), and by the children themselves in all other cases; a health professional was always present to provide assistance. As expected, JRA patients with a systemic or polyarticular disease onset had higher scores than those with a pauciarticular onset, and there were statistically significant differences in disability index values between patients from different Steinbrocker functional classes. The instrument showed good reproducibility in a test-retest over a two-week period, a high correlation between the child and parent scores, excellent internal reliability, and good convergent and discriminant validity.

A multicenter study on insulin-like growth factor-I serum levels in children with chronic inflammatory diseases.

OBJECTIVE: To study insulin-like factor-I (IGF-I) levels in children and adolescents with connective tissue diseases (CTDs), compare them with values obtained in normal controls, and correlate them with age, sex, steroid treatment, and inflammatory parameters. METHODS: A multicenter, cross-sectional study was performed in 3 Italian pediatric rheumatology centers. The subjects studied comprised 117 patients with juvenile arthritis (53 systemic, 25 pauciarticular and 17 polyarticular) and other CTDs (22), and 78 children without inflammatory conditions. IGF-I levels were measured by radioimmunoassay after acid-ethanol extraction. RESULTS: Mean IGF-I serum levels were 167.6 ng/ml (+/- 132.5) in patients and 214.4 (+/- 142.8) in controls. A significant correlation was found between IGF-I levels and age in the controls (P = 0.001), but not in the patients. Covariance analysis with age as the covariate showed significantly lower IGF-I levels in the patient group (P = 0.001). No significant correlation was found between IGF-I levels and the total quantity of steroid taken. Multiple regression analysis showed that IGF-I levels were inversely correlated with the ESR (P = 0.0001) and positively correlated with age (P = 0.0002) and sex (P = 0.021) in the patient group. CONCLUSION: IGF-I serum levels are decreased in patients with CTDs; inflammation could play a major role.

Oral versus intramuscular methotrexate in juvenile chronic arthritis. Italian Pediatric Rheumatology Study Group.

OBJECTIVE: To compare the efficacy and safety of methotrexate (MTX) after oral and intramuscular administration in children with juvenile chronic arthritis (JCA). METHODS: Pediatric rheumatology centers in Italy participated in this short-term, prospective, open trial. Each investigator was allowed to choose the oral or intramuscular route of administration according to his personal preference in everyday clinical practice. Patients enrolled by each center were given MTX through the same method of administration. All patients received 10 mg/m2 of MTX each week for six months. RESULTS: A total of 257 patients with JCA (127 treated orally and 130 intramuscularly) were enrolled in the trial by 11 Italian centers. The response rate after 6 months of MTX therapy was 58% in the oral and 61% in the intramuscular cohort. The frequency of adverse side effects did not differ significantly between the two treatment groups. CONCLUSION: The results of this study suggest that MTX at the conventional dose regimen is equally effective and has a similar safety profile in children with JCA when administered orally or by intramuscular injections.

The Italian version of the Childhood Health Assessment Questionnaire (CHAQ) and the Child Health Questionnaire (CHQ).

We report herein the results of the cross-cultural adaptation and validation into the Italian language of the parent's version of two health related quality of life instruments. The Childhood Health Assessment Questionnaire (CHAQ) is a disease specific health instrument that measures functional ability in daily living activities in children with juvenile idiopathic arthritis (JIA). The Child Health Questionnaire (CHQ) is a generic health instrument designed to capture the physical and psychosocial well-being of children independently from the underlying disease. The Italian CHAQ was already published in the literature and was therefore revalidated while the Italian CHQ was fully cross culturally adapted with 3 forward and 3 backward translations, and than validated. A total of 1,192 subjects were enrolled: 404 patients with JIA (16% systemic onset, 31% polyarticular onset, 21% extended oligoarticular subtype, and 32% persistent oligoarticular subtype) and 788 healthy children. The CHAQ clinically discriminated between healthy subjects and JIA patients, with the systemic, polyarticular and extended oligoarticular subtypes having a higher degree of disability, pain, and a lower overall well-being when compared to their healthy peers. Also the CHQ clinically discriminated between healthy subjects and JIA patients, with the systemic onset, polyarticular onset and extended oligoarticular subtypes having a lower physical and psychosocial well-being when compared to their healthy peers. In conclusion the Italian version of the CHAQ-CHQ are reliable, and valid tools for the functional, physical and psychosocial assessment of children with JIA.

[Anti-chromatin antibodies in juvenile rheumatoid arthritis]. / Anticorpi anti-cromatina in corso di artrite reumatoide giovanile.

OBJECTIVE: to evaluate the prevalence and clinical significance of anti-chromatin antibodies (Abs) in juvenile rheumatoid arthritis (JRA). METHODS: IgG anti-chromatin Abs were detected by an enzyme-linked immunosorbent assay (ELISA), in sera of 94 children with JRA (10 children with systemic, 38 with polyarticular and 46 with oligoarticular disease onset). As control group, 33 age- and-sex-matched healthy children (HC) were also examined. RESULTS: Abs to chromatin were detected in 24/94 (25.5%) of children suffering from JRA. Particularly, the higher prevalence of anti-chromatin Abs has been found in children with oligoarticular (30,4%) and polyarticular (23.7%) onset JRA. In these groups Abs titers were significantly higher compared to systemic JRA and HC (p=0.003). Anti-chromatin Abs were observed more frequently in patients with oligoarticular disease and chronic uveitis (21.7%). Furthermore, higher levels of anti-chromatin Abs has been found in all the patients treated with anti-TNF-alpha therapy (p< 0.0001). CONCLUSIONS: our results confirm previous data about the prevalence of anti-chromatin Abs in JRA. These Abs were significantly higher in the group of patients with oligoarticular onset with past or present history of ocular involvement and in the group with polyarticular JRA treated with biologic therapy. A long-term follow-up study could be useful to evaluate the potential utility of these autoantibodies.