@article {10579, title = {Flares After Withdrawal of Biologic Therapies in Juvenile Idiopathic Arthritis: Clinical and Laboratory Correlates of Remission Duration.}, journal = {Arthritis Care Res (Hoboken)}, volume = {70}, year = {2018}, month = {2018 Jul}, pages = {1046-1051}, abstract = {

OBJECTIVE: To assess the time in remission after discontinuing biologic therapy in patients with juvenile idiopathic arthritis (JIA).

METHODS: We enrolled 135 patients followed in 3 tertiary-care centers. The primary outcome was to assess, once remission was achieved, the time in remission up to the first flare after discontinuing treatment. Mann-Whitney U test, Wilcoxon{\textquoteright}s signed rank test for paired samples, chi-square tests, and Fisher{\textquoteright}s exact test were used to compare data. Pearson{\textquoteright}s and Spearman{\textquoteright}s correlation tests were used to determine correlation coefficients for different variables. To identify predictors of outcome, Cox regression model and Kaplan-Meier curves were constructed, each one at the mean of entered covariates.

RESULTS: The majority of enrolled patients flared after stopping treatment with biologics (102 of 135, 75.6\%) after a median followup time in remission off therapy of 6 months (range 3-109 months). A higher probability of maintaining remission after discontinuing treatment was present in systemic-onset disease compared to the rest of the JIA patients (Mantel-Cox χ = 8.31, P < 0.004). In analysis limited to children with JIA with polyarticular and oligoarticular disease, patients who received biologics >2 years after achieving remission had a higher probability of maintaining such remission off therapy (mean {\textpm} SD 18.64 {\textpm} 3.3 months versus 11.51 {\textpm} 2.7 months [P < 0.009]; Mantel-Cox χ = 9.06, P < 0.002). No other clinical variable was significantly associated with a long-lasting remission.

CONCLUSION: Children with oligoarticular and polyarticular JIA who stop treatment before 2 years from remission have a higher chance of relapsing after biologic withdrawal.

}, issn = {2151-4658}, doi = {10.1002/acr.23435}, author = {Simonini, Gabriele and Ferrara, Giovanna and Pontikaki, Irene and Scoccimarro, Erika and Giani, Teresa and Taddio, Andrea and Meroni, Pier Luigi and Cimaz, Rolando} } @article {8483, title = {Describing Kawasaki shock syndrome: results from a retrospective study and literature review.}, journal = {Clin Rheumatol}, volume = {36}, year = {2017}, month = {2017 Jan}, pages = {223-228}, abstract = {

Kawasaki shock syndrome (KSS) is a rare manifestation of Kawasaki disease (KD) characterized by systolic hypotension or clinical signs of poor perfusion. The objectives of the study are to describe the main clinical presentation, echocardiographic, and laboratory findings, as well as the treatment options and clinical outcomes of KSS patients when compared with KD patients. This is a retrospective study. All children referred to two pediatric rheumatology units from January 1, 2012, to December 31, 2014, were enrolled. Patients were divided into patients with or without KSS. We compared the two groups according to the following variables: sex, age, type of KD (classic, with less frequent manifestations, or incomplete), clinical manifestations, cardiac involvement, laboratory findings, therapy administered, response to treatment, and outcome. Eighty-four patients with KD were enrolled. Of these, five (6~\%) met the criteria for KSS. Patients with KSS had higher values of C-reactive protein (p = 0.005), lower hemoglobin levels (p = 0.003); more frequent hyponatremia (p = 0.004), hypoalbuminemia (p = 0.004), and coagulopathy (p = 0.003); and increase in cardiac troponins (p = 0.000). Among the KSS patients, three had a coronary artery involvement, but none developed a permanent aneurysm. Intravenous immunoglobulin resistance was more frequent in the KSS group, although not significantly so (3/5, 60~\% vs. 23/79, 30~\%, P = NS). None of the five cases was fatal, and all recovered without sequelae. KSS patients are more likely to have higher rates of cardiac involvement. However, most cardiovascular abnormalities resolved promptly with therapy.

}, keywords = {C-Reactive Protein, Child, Child, Preschool, Echocardiography, Female, Heart Failure, Hemoglobins, Humans, Immunoglobulins, Intravenous, Male, Mucocutaneous Lymph Node Syndrome, Retrospective Studies, Shock, Syndrome}, issn = {1434-9949}, doi = {10.1007/s10067-016-3316-8}, author = {Taddio, Andrea and Rossi, Eleonora Dei and Monasta, Lorenzo and Pastore, Serena and Tommasini, Alberto and Lepore, Loredana and Bronzetti, Gabriele and Marrani, Edoardo and Mottolese, Biancamaria D{\textquoteright}Agata and Simonini, Gabriele and Cimaz, Rolando and Ventura, Alessandro} } @article {10523, title = {Predictors of Relapse after Discontinuing Systemic Treatment in Childhood Autoimmune Chronic Uveitis.}, journal = {J Rheumatol}, volume = {44}, year = {2017}, month = {2017 06}, pages = {822-826}, abstract = {

OBJECTIVE: To identify clinical predictors of relapse in childhood autoimmune chronic uveitis after stopping systemic treatment.

METHODS: A retrospective, multicenter, cohort study.

RESULTS: Ninety-four children in remission, receiving no treatments and with at least a 6-month followup, were enrolled. A higher probability of maintaining remission after discontinuing treatment was shown in idiopathic compared with juvenile idiopathic arthritis uveitis (Mantel-Cox chi-square = 23.21) if inactivity had been obtained within 6 months from starting systemic treatment (Mantel-Cox chi-square = 24.17) and by antitumor necrosis factor-α treatment (Mantel-Cox chi-square = 6.43).

CONCLUSION: Type of disease, time, and type of systemic therapy to achieve inactivity predict different duration of uveitis remission after treatment withdrawal.

}, keywords = {Adolescent, Antirheumatic Agents, Autoimmune Diseases, Child, Child, Preschool, Female, Humans, Male, Predictive Value of Tests, Recurrence, Retrospective Studies, Treatment Outcome, Uveitis, Withholding Treatment}, issn = {0315-162X}, doi = {10.3899/jrheum.161336}, author = {Simonini, Gabriele and Bracaglia, Claudia and Cattalini, Marco and Taddio, Andrea and Brambilla, Alice and de Libero, Cinzia and Pires Marafon, Denise and Caputo, Roberto and Cimaz, Rolando} } @article {8299, title = {Recent advances in the use of Anti-TNFα therapy for the treatment of juvenile idiopathic arthritis.}, journal = {Expert Rev Clin Immunol}, volume = {12}, year = {2016}, month = {2016 Jun}, pages = {641-9}, abstract = {

Juvenile Idiopathic Arthritis (JIA) encompasses a group of diseases of unknown etiology having in common arthritis in at least 1 joint that persists for 6 weeks and begins before 16 years of age, with other conditions excluded. With a prevalence of 1 per 1,000 children in the USA, JIA is the most common pediatric rheumatic illness and a major cause of acquired childhood disability. During the last 20 years, the advent of host immune response modifiers known as biologic agents, in particular the anti-TNFα agents (etanercept, infliximab, adalimumab), which directly inhibit the action of pro-inflammatory mediators, has revolutionized the treatment and the expected outcome of JIA. This article highlights treatment indications of anti-TNFα drugs and their more frequent side effects in JIA patients.

}, issn = {1744-8409}, doi = {10.1586/1744666X.2016.1146132}, author = {Taddio, Andrea and Cattalini, Marco and Simonini, Gabriele and Cimaz, Rolando} } @article {1991, title = {Safety and efficacy of infliximab and adalimumab for refractory uveitis in juvenile idiopathic arthritis: 1-year followup data from the Italian Registry.}, journal = {J Rheumatol}, volume = {40}, year = {2013}, month = {2013 Jan}, pages = {74-9}, abstract = {

OBJECTIVE: To evaluate safety and efficacy of adalimumab (ADA) and infliximab (IFX) for the treatment of juvenile idiopathic arthritis-related anterior uveitis (JIA-AU).

METHODS: Starting January 2007, patients with JIA-AU treated with IFX and ADA were managed by a standard protocol and data were entered into the National Italian Registry (NIR). At baseline, all patients were refractory to standard immunosuppressive treatment and/or were corticosteroid-dependent. Data recorded every 3 months included uveitis course, number/type of ocular complications, drug-related adverse events (AE), treatment change or withdrawal, and laboratory measures. Data of patients treated for at least 1 year were retrieved from the NIR and analyzed using descriptive statistics. Treatment efficacy was based on change in uveitis course and in number of ocular complications.

RESULTS: Up to December 2009, data for 108 patients with JIA-AU treated with anti-tumor necrosis factor-α agents were recorded in the NIR and data from 91, with at least 12 months{\textquoteright} followup, were included in the study. Forty-eight patients were treated with IFX, 43 with ADA. Forty-seven patients (55.3\%) achieved remission of AU, 28 (32.9\%) had recurrent AU, and 10 (11.8\%) maintained a chronic course. A higher remission rate was observed with ADA (67.4\% vs 42.8\% with IFX; p = 0.025). Ocular complications decreased from 0.47 to 0.32 per subject. Five patients experienced resolution of structural complications. No patient reported serious AE; 8 (8.8\%) experienced 11 minor AE (9 with IFX, 2 with ADA).

CONCLUSION: IFX and ADA appear to be effective and safe for treatment of refractory JIA-related uveitis, with a better performance of ADA in the medium-term period.

}, keywords = {Adolescent, Antibodies, Monoclonal, Antibodies, Monoclonal, Humanized, Antirheumatic Agents, Arthritis, Juvenile, Child, Child, Preschool, Female, Follow-Up Studies, Humans, Infant, Italy, Male, Registries, Treatment Outcome, Tumor Necrosis Factor-alpha, Uveitis}, issn = {0315-162X}, doi = {10.3899/jrheum.120583}, author = {Zannin, Maria E and Birolo, Carolina and Gerloni, Valeria M and Miserocchi, Elisabetta and Pontikaki, Irene and Paroli, Maria P and Bracaglia, Claudia and Shardlow, Alison and Parentin, Fulvio and Cimaz, Rolando and Simonini, Gabriele and Falcini, Fernanda and Corona, Fabrizia and Viola, Stefania and De Marco, Riccardo and Breda, Luciana and La Torre, Francesco and Vittadello, Fabio and Martini, Giorgia and Zulian, Francesco} } @article {1855, title = {Childhood chronic anterior uveitis associated with vernal keratoconjunctivitis (VKC): successful treatment with topical tacrolimus. Case series.}, journal = {Pediatr Rheumatol Online J}, volume = {9}, year = {2011}, month = {2011}, pages = {34}, abstract = {

Uveitis treatment involves topical corticosteroids along with cycloplegic-mydriatics. Particularly severe cases may require systemic corticosteroids and immunosuppressive drugs. Vernal keratoconjunctivitis (VKC) treatment consists of a brief period of topical corticosteroids and/or cyclosporine. In patients refractory to traditional treatment, the use of 0.1\% topical ophtalmic FK- 506 (tacrolimus) ointment has been occasionally reported.This is the first report of the coexistence of uveitis and VKC. The documented response to topical tacrolimus eyedrop of uveitis and VKC is also of interest, in particular since to our knowledge there are no published reports on its clinical use in uveitis.

}, issn = {1546-0096}, doi = {10.1186/1546-0096-9-34}, author = {Taddio, Andrea and Cimaz, Rolando and Caputo, Roberto and de Libero, Cinzia and Di Grande, Laura and Simonini, Gabriele and Mori, Francesca and Novembre, Elio and Pucci, Neri} } @article {1764, title = {Usefulness of wireless capsule endoscopy for detecting inflammatory bowel disease in children presenting with arthropathy.}, journal = {Eur J Pediatr}, volume = {170}, year = {2011}, month = {2011 Oct}, pages = {1343-7}, abstract = {

Inflammatory bowel disease (IBD) is a cause of chronic intestinal inflammation in children. In a subset of patients affected by IBD, arthropathy may be the leading presenting sign. In the past years, remarkable advances in gastrointestinal endoscopy techniques have been achieved; recently, the development of capsule endoscopy (CE) provided a non-invasive method for the complete endoscopic evaluation, including small bowel assessment. We report three children suffering from IBD but presenting with articular complaints in whom CE was a useful tool for detecting gut inflammation. Patients were investigated with the wireless CE: PillCam SB2 (Given Imaging, Yoqneam, Israel) capsule, the second-generation capsule, was used in our paediatric patients. Three patients were initially evaluated for arthropathy. Enteropathic arthritis was suspected for gastrointestinal symptoms and/or persistence of inflammatory markers elevation. In one of these children, conventional endoscopy was refused by parents, while in the other two children, CE was proposed as first-line diagnostic tool. In all patients, CE revealed to be safe and provided information that led to diagnosis. Paediatric rheumatologists should consider CE as a valid, non-invasive tool, eventually first level diagnostic approach in order to evaluate the presence of IBD in children presenting with chronic articular complaints.

}, keywords = {Adolescent, Arthritis, Juvenile, Capsule Endoscopy, Child, Colitis, Ulcerative, Colon, Crohn Disease, Diagnosis, Differential, Follow-Up Studies, Humans, Inflammatory Bowel Diseases, Intestine, Small, Male, Predictive Value of Tests, Sensitivity and Specificity, Severity of Illness Index, Treatment Outcome}, issn = {1432-1076}, doi = {10.1007/s00431-011-1505-7}, author = {Taddio, Andrea and Simonini, Gabriele and Lionetti, Paolo and Lepore, Loredana and Martelossi, Stefano and Ventura, Alessandro and Cimaz, Rolando} } @article {1694, title = {Abatacept improves health-related quality of life, pain, sleep quality, and daily participation in subjects with juvenile idiopathic arthritis.}, journal = {Arthritis Care Res (Hoboken)}, volume = {62}, year = {2010}, month = {2010 Nov}, pages = {1542-51}, abstract = {

OBJECTIVE: To assess health-related quality of life (HRQOL) in abatacept-treated children/adolescents with juvenile idiopathic arthritis (JIA).

METHODS: In this phase III, double-blind, placebo-controlled trial, subjects with active polyarticular course JIA and an inadequate response/intolerance to >=1 disease-modifying antirheumatic drug (including biologics) received abatacept 10 mg/kg plus methotrexate (MTX) during the 4-month open-label period (period A). Subjects achieving the American College of Rheumatology Pediatric 30 criteria for improvement (defined "responders") were randomized to abatacept or placebo (plus MTX) in the 6-month double-blind withdrawal period (period B). HRQOL assessments included 15 Child Health Questionnaire (CHQ) health concepts plus the physical (PhS) and psychosocial summary scores (PsS), pain (100-mm visual analog scale), the Children{\textquoteright}s Sleep Habits Questionnaire, and a daily activity participation questionnaire.

RESULTS: A total of 190 subjects from period A and 122 from period B were eligible for analysis. In period A, there were substantial improvements across all of the CHQ domains (greatest improvement was in pain/discomfort) and the PhS (8.3 units) and PsS (4.3 units) with abatacept. At the end of period B, abatacept-treated subjects had greater improvements versus placebo in all domains (except behavior) and both summary scores. Similar improvement patterns were seen with pain and sleep. For participation in daily activities, an additional 2.6 school days/month and 2.3 parents{\textquoteright} usual activity days/month were gained in period A responders with abatacept, and further gains were made in period B (1.9 versus 0.9 [P = 0.033] and 0.2 versus -1.3 [P = 0.109] school days/month and parents{\textquoteright} usual activity days/month, respectively, in abatacept- versus placebo-treated subjects).

CONCLUSION: Improvements in HRQOL were observed with abatacept, providing real-life tangible benefits to children with JIA and their parents/caregivers.

}, keywords = {Adolescent, Arthritis, Juvenile, Child, Double-Blind Method, Female, Health Status, Humans, Immunoconjugates, Male, Pain, Quality of Life, Questionnaires, Sleep Stages}, issn = {2151-4658}, doi = {10.1002/acr.20283}, author = {Ruperto, Nicolino and Lovell, Daniel J and Li, Tracy and Sztajnbok, Flavio and Goldenstein-Schainberg, Claudia and Scheinberg, Morton and Penades, Inmaculada Calvo and Fischbach, Michael and Alcala, Javier Orozco and Hashkes, Philip J and Hom, Christine and Jung, Lawrence and Lepore, Loredana and Oliveira, Sheila and Wallace, Carol and Alessio, Maria and Quartier, Pierre and Cortis, Elisabetta and Eberhard, Anne and Simonini, Gabriele and Lemelle, Irene and Chalom, Elizabeth Candell and Sigal, Leonard H and Block, Alan and Covucci, Allison and Nys, Marleen and Martini, Alberto and Giannini, Edward H} } @article {1680, title = {Defective FOXP3 expression in patients with acute Kawasaki disease and restoration by intravenous immunoglobulin therapy.}, journal = {Clin Exp Rheumatol}, volume = {28}, year = {2010}, month = {2010 Jan-Feb}, pages = {93-7}, abstract = {

OBJECTIVES: The aims of this study were: 1) to investigate forkhead box P3 (FOXP3) expression in patients with Kawasaki disease (KD), exploring possible differences during the acute phase and after defervescence; 2) to evaluate a possible association of the FOXP3 single nucleotide polymorphism (SNP) 543 (SNP ID: rs2232367) with KD.

METHODS: FOXP3 expression was evaluated on 8 children with KD and 15 healthy children by flow cytometry and Real-Time polymerase chain reaction (RT-PCR). FOXP3 SNP 543 was genotyped by denaturing high-performance liquid chromatography (DHPLC) and sequencing on DNA samples from 58 additional children with KD and 114 healthy donors.

RESULTS: The frequencies of CD4+CD25 +FOXP3+ regulatory T cells were significantly (p=0.0002) lower during the acute phase of KD than in sex- and age-matched healthy donors (median \% + SD: 4.8+/-1.3 vs. 7.7+/-1.7) and a similar tendency was revealed for FOXP3 mRNA transcripts (p<0.0001). FOXP3 expression increased significantly, at both protein and mRNA levels, after intravenous immunoglobulin (IVIG) therapy treatment and achieving complete remission of disease (at least 48 hrs; median 9.5 days, range 2-30). Of the 58 patients screened, only one female subject (1.7\%) carried the presence of 543 SNP in heterozygosis (C>T; for a total of 1 allele out of 88), with no difference between KD patients and controls (0.0\%, 0/203 alleles).

CONCLUSIONS: Our data reinforce the notion of an impaired immunoregulation in KD, suggesting also a role of IVIG treatment in modifying the Treg compartment. FOXP3 SNP 543 does not seem to be involved in susceptibility to KD in Italian children.

}, keywords = {Acute Disease, Child, Child, Preschool, Female, Flow Cytometry, Forkhead Transcription Factors, Genotype, Humans, Immunoglobulins, Intravenous, Infant, Italy, Male, Mucocutaneous Lymph Node Syndrome, Polymorphism, Single Nucleotide, Reverse Transcriptase Polymerase Chain Reaction, RNA, Messenger, T-Lymphocytes, Regulatory}, issn = {0392-856X}, author = {Olivito, Biagio and Taddio, Andrea and Simonini, Gabriele and Massai, Cristina and Ciullini, Sara and Gambineri, Eleonora and de Martino, Maurizio and Azzari, Chiara and Cimaz, Rolando} }