Rheumatoid Arthritis: Martini G

Martini G, Zulian F. · Department of Pediatric Rheumatology, University of Padua, Italy. · Expert Opin Pharmacother. · Pubmed #16503811 No free full text.

Abstract: Juvenile idiopathic arthritis is the most common rheumatic disease in children. The management of juvenile idiopathic arthritis has improved in recent decades, and morbidity due to the disease is significantly decreased. In particular, the use of more effective drugs and their combination has changed the course of the disease in many patients. The increasing knowledge of inflammation mechanisms has lead to the development of new agents that target specific cytokines interfering with the inflammatory cascade. In particular, anti-TNF agents seem effective: etanercept is the only one licensed for juvenile idiopathic arthritis, and Phase III trials on two other anti-TNF agents, infliximab and adalimumab, are ongoing. This review discusses the current practice in the medical management of juvenile idiopathic arthritis, and potential new agents are discussed.

Zulian F, Martini G, Gobber D, Plebani M, Zacchello F, Manners P. · Rheumatology Unit, Department of Paediatrics, University Hospital of Padua, Via Giustiniani 3, 35128 Padova, Italy. · Rheumatology (Oxford). · Pubmed #15252213 links to  free full text

Abstract: OBJECTIVE: Pharmacokinetic studies have shown that the biological effect of triamcinolone acetonide (TA) is equivalent to that of triamcinolone hexacetonide (TH), if used at double the dosage. In this study we compared the efficacy of intra-articular TA at a dose twice that of TH in symmetrically involved joints, in children with juvenile idiopathic arthritis (JIA). METHOD: Children with active arthritis and a similar degree of inflammation in two symmetrical joints were enrolled in the study. The symmetry was assessed by both clinical examination and synovial fluid analysis. The dose given was 1 mg/kg up to 40 mg of TH or 2.0 mg/kg up to 80 mg of TA. The identity of injected compound was blinded to the patient and to the physician. RESULTS: Thirty-seven patients, 30 female, seven male, with JIA, entered the study. A total of 86 joints were injected. Twenty-one (53.8%) of the joints injected with TA relapsed first compared with only six (15.4%) of the joints injected with TH. In three (7.7%) relapse occurred simultaneously. Nine (23%) were still in remission after 24-month follow-up. The percentage of joints with lasting remission was higher with TH than with TA (80 vs 47.5% after 12 months and 63.6 vs 32.4% after 24 months, respectively; log rank test P = 0.003). CONCLUSION: Even when TA is given at higher doses, TH is more effective and should be considered the drug of choice for intra-articular treatment of JIA.

Zulian F, Martini G, Gobber D, Agosto C, Gigante C, Zacchello F. · Department of Paediatrics, University of Padua, Italy. · Rheumatology (Oxford). · Pubmed #12810938 links to  free full text

Abstract: OBJECTIVE: To compare the efficacy and safety of intra-articular triamcinolone hexacetonide (TH) and triamcinolone acetonide (TA) in children with oligoarticular juvenile idiopathic arthritis (JIA). METHODS: One hundred and thirty joints of 85 patients undergoing intra-articular injections were randomly treated with either TH or TA depending on the availability of the drug. The efficacy of both treatments was evaluated prospectively in a blinded fashion. A good response was defined as a decrease in the articular score of > or =60% from baseline. Clinical, laboratory and immunological variables were noted in order to examine possible factors, other than treatment, predictive of the result. RESULTS: Seventy injections were performed using TH and 60 with TA. The two groups were comparable for clinical, immunological and laboratory characteristics. The rate of response was significantly higher with TH than with TA: 81.4% vs 53.3% (P = 0.001) at 6 months, 67.1 vs 43.3% (P = 0.006) at 12 months, and 60 vs 33.3% (P = 0.002) at 24 months. CONCLUSION: At comparable doses TH appeared to be much more effective than TA for intra-articular use, in both short- and long-term follow-up. This result was not affected by disease duration or degree of local and systemic inflammation.

Vitale A, La Torre F, Martini G, Calcagno G, Fede C, Conti G, Chimenz R, Zulian F. · Department of Paediatrics, Rheumatology Unit, University of Messina, Messina, Italy. · J Paediatr Child Health. · Pubmed #19317761 No free full text.

Abstract: In developed countries, scurvey is quite rare and can be seen in children with severely restricted diets, related to psychiatric or developmental problems. Clinical presentation can include arthralgias/arthritis, myalgias, hemarthrosis, purpura and ecchymosis. We report two cases of nutritional vitamin C deficiency, who have been misdiagnosed as having rheumatologic diseases, and promptly resolved with vitamin C treatment. Both patents did not have the classic radiological features described in scurvey, such as the Wimberger ring or the white lines of Frankel. Magnetic resonance imaging clearly showed areas of hemorrhage at bony and subperiasteal level. This imaging procedure, therefore, should be recommended especially in the doubtful cases. The two patients described herein should alert pediatricians to consider scurvey although rare, as a potential source of "rheumatological" manifestations in children, especially in the industrialized countries where in appropriate vitamin intake is often underestimated.

Zannin ME, Martini G, Buscain I, Cermàkovà I, Suppiej A, Manara R, Zulian F. · Department of Pediatrics, Via Giustiniani 3, 35128 Padua, Italy. · Br J Ophthalmol. · Pubmed #19244028 No free full text.

This publication has no abstract.

Martini G, Cabrelle A, Calabrese F, Carraro S, Scquizzato E, Teramo A, Facco M, Zulian F, Agostini C. · Pediatric Rheumatology Unit, University of Padova, Italy. · Clin Immunol. · Pubmed #18760678 No free full text.

Abstract: In order to evaluate the role of CXCR6/CXCL16 in driving lymphocyte migration into inflamed joints of children with oligoarticular Juvenile Idiopathic Arthritis (JIA) we analysed CXCR6 expression and functional capability in lymphocytes from synovial fluid (SF) by flow cytometry, by real-time polymerase chain reaction (RT-PCR) and migration assays. Furthermore, CXCR6 and CXCL16 expression in synovial tissue (ST) was analysed by immunohistochemistry. T cells isolated from SF of patients with JIA expressed CXCR6 which was functionally active as shown by chemotactic assays. The same cells expressed CXCR3 and it exerted a migratory activity in response to CXCL10. CXCL16 and CXCR6 were intensively expressed on the synovium cells, respectively on macrophages, synoviocytes and endothelial cells and on lymphocytes, synoviocytes and endothelial cells. Taken together, these data suggest that CXCR6 and CXCR3 act coordinately with respective ligands and are involved in the pathophysiology of JIA-associated inflammatory processes.

Cimaz R, Cazalis MA, Reynaud C, Gerloni V, Zulian F, Biggioggero M, Martini G, Pontikaki I, Fantini F, Mougin B, Miossec P. · Unité Mixte Hospices Civils de Lyon-BioMérieux, Lyon, France. · Ann Rheum Dis. · Pubmed #17324969 No free full text.

Abstract: OBJECTIVE: To investigate the genetic contribution of cytokine gene polymorphisms (interleukin 1 (IL1) and tumour necrosis factor alpha (TNFalpha)) on disease phenotype and on response to TNF-blocking agents in a population of patients with juvenile idiopathic arthritis (JIA). METHODS: A cohort of 107 consecutive patients with JIA who were receiving treatment with anti-TNF agents was enrolled in this study. Analysis of genetic polymorphisms for IL1B +3954, IL1RA +2018, TNFalpha -238 and TNFalpha -308 was performed by enzyme-linked oligo sorbent assay, and compared with those obtained from 630 healthy Caucasians and 263 adult patients with rheumatoid arthritis. Relevant demographic, clinical and laboratory data were collected from clinical charts and entered into a customised database, and chi(2) analysis was performed to compare cytokine polymorphisms with disease type according to the International League of Associations for Rheumatology criteria, presence of uveitis, rheumatoid factor and anti-nuclear antibody positivity, erosive disease, frequency of adverse effects to anti-TNF and clinical response after 3 months. RESULTS: The T/T genotype of the IL1B +3954 polymorphism was absent in patients with JIA and present in 5% of controls (p = 0.015). No significant correlation was found between the studied polymorphisms and clinical or laboratory variables considered. Clinical response to TNF inhibitors at 3 months was not associated with the genetic polymorphisms considered. CONCLUSION: In our cohort, the absence of the rare IL1B +3954 gene polymorphism was associated with JIA, but without specificity to particular disease phenotypes. The TNF and IL1 gene polymorphism studied did not seem to be associated with response to anti-TNF treatment.

Toledo MM, Martini G, Gigante C, Da Dalt L, Tregnaghi A, Zulian F. · Department of Pediatrics, University of Padua, Padua, Italy. · J Rheumatol. · Pubmed #16881093 No free full text.

Abstract: OBJECTIVE: To evaluate the longterm efficacy and safety of arthroscopic synovectomy (AS) in children with oligoarticular juvenile idiopathic arthritis (JIA). METHODS: Patients with oligoarticular JIA and persistent monoarticular involvement, refractory to nonsteroidal antiinflammatory drugs (NSAID) and/or intraarticular corticosteroid (IAC) treatment underwent AS followed, one month later, by IAC. The efficacy of AS was prospectively evaluated, and a good response was defined as absence of synovitis or > or = 60% decrease in articular score from baseline. Clinical, laboratory, and radiological variables (radiographs, ultrasound, magnetic resonance imaging) were noted to examine possible factors predictive of the result. RESULTS: Twenty-two patients with JIA (15 female, 7 male) entered the study. Age at disease onset was 77 months (range 13-168). Mean disease duration at the time of AS was 50 months (3-324). Nineteen knees, 2 temporomandibular joints, and one shoulder were treated; the mean followup was 57 months (12-168). Thirty-six percent of patients relapsed within 12 months of the procedure, 14% within 24 months, and 14% thereafter. Eight patients (36%) remain in remission after a mean 65 months' followup. Variables found to be predictive of good response were persistent monoarticular course (p = 0.004), short disease duration at the time of AS (p = 0.03), and normal erythrocyte sedimentation rate and C-reactive protein at baseline (p = 0.008 and 0.01, respectively). CONCLUSION: AS is a safe but only partially effective procedure in patients with oligoarticular JIA. Best results are achieved early in the disease course in children with persistent monoarticular involvement and no evidence of systemic inflammation.

Martini G, Zulian F, Calabrese F, Bortoli M, Facco M, Cabrelle A, Valente M, Zacchello F, Agostini C. · Department of Paediatrics, Padua University School of Medicine, Italy. · Arthritis Res Ther. · Pubmed #15743470 links to  free full text

Abstract: The accumulation of T cells in the synovial membrane is the crucial step in the pathophysiology of the inflammatory processes characterizing juvenile idiopathic arthritis (JIA). In this study, we evaluated the expression and the pathogenetic role in oligoarticular JIA of a CXC chemokine involved in the directional migration of activated T cells, i.e. IFNgamma-inducible protein 10 (CXCL10) and its receptor, CXCR3. Immunochemistry with an antihuman CXCL10 showed that synovial macrophages, epithelial cells, and endothelial cells bear the chemokine. By flow cytometry and immunochemistry, it has been shown that CXCR3 is expressed at high density by virtually all T lymphocytes isolated from synovial fluid (SF) and infiltrating the synovial membrane. Particularly strongly stained CXCR3+ T cells can be observed close to the luminal space and in the perivascular area. Furthermore, densitometric analysis has revealed that the mRNA levels for CXCR3 are significantly higher in JIA patients than in controls. T cells purified from SF exhibit a definite migratory capability in response to CXCL10. Furthermore, SF exerts significant chemotactic activity on the CXCR3+ T-cell line, and this activity is inhibited by the addition of an anti-CXCL10 neutralizing antibody. Taken together, these data suggest that CXCR3/CXCL10 interactions are involved in the pathophysiology of JIA-associated inflammatory processes, regulating both the activation of T cells and their recruitment into the inflamed synovium.

Martini G, Tregnaghi A, Bordin T, Visentin MT, Zulian F. · Rheumatology Unit, Department of Pediatrics, University of Padua, Padua, Italy. · J Rheumatol. · Pubmed #14719222 No free full text.

This publication has no abstract.

Zulian F, Martini G, Falcini F, Gerloni V, Zannin ME, Pinello L, Fantini F, Facchin P. · Department of Pediatrics, University of Padua, Padua, Italy. · J Rheumatol. · Pubmed #12415607 No free full text.

Abstract: OBJECTIVE: To determine whether demographic, clinical, and laboratory variables at onset of arthritis can predict the development and the severity of anterior uveitis (AU) in oligoarticular juvenile idiopathic arthritis (JIA). METHODS: In a retrospective study, a cohort of 366 patients with oligoarticular onset JIA from 3 pediatric rheumatology centers were evaluated. Patients were classified in 3 groups: severe uveitis (SU) with a mean >/= 2 uveitis relapses/year with complications or need for immunosuppressive therapy; mild uveitis (MU) with a mean </= 1 uveitis relapse/year with no complications; and no uveitis. Variables that were significant with univariate tests or were clinically relevant for each outcome underwent multivariate logistic regression analysis. RESULTS: There were 316 patients available for analyses: 66 in the SU group, 64 in the MU group, and 186 in the no uveitis group. Multivariate analysis showed the following factors to be significant as predictors of AU onset: low age at onset (OR 0.96), a2-globulin plasma concentration (OR 1.34), and HLA-A19 (OR 2.87), B22 (OR 4.51) and DR9 (OR 2.33), while HLA-DR1 conferred protection (OR 0.13). This model was not good in predicting which patient would develop uveitis (sensitivity 55%, specificity 26%). Time interval between onset of arthritis and the first AU and elevated a2-globulin level in the serum were the best predictors of AU severity (OR 1.62 and 0.85, respectively). When applied prospectively, the model revealed good sensitivity (89.2%), specificity (76.1%), and efficiency (86.3%). CONCLUSION: Clinical and laboratory variables measurable at onset of arthritis can be used to predict severity of the course of AU in oligoarticular JIA, but not its onset. More accurate prediction can shorten or lengthen the intervals between ophthalmologic evaluations and can change the therapeutic approach undertaken on the basis of expected disease severity.

Avcin T, Cimaz R, Falcini F, Zulian F, Martini G, Simonini G, Porenta-Besic V, Cecchini G, Borghi MO, Meroni PL. · Department of Paediatrics, University of Ljubljana, Slovenia, Italy. · Ann Rheum Dis. · Pubmed #12079901 links to  free full text

Abstract: BACKGROUND: Antibodies against cyclic citrullinated peptide (anti-CCP) are considered to be specific for rheumatoid arthritis (RA). OBJECTIVE: To assess the clinical significance of anti-CCP in a cohort of patients with juvenile idiopathic arthritis (JIA). METHODS: Anti-CCP were tested by an enzyme linked immunosorbent assay (ELISA) in serum samples from 109 patients with JIA (30 boys, 79 girls), with a mean age of 8.7 years (range 0.6-20.3) and mean disease duration of 3.6 years (range 3 months to 15.6 years). As control groups, anti-CCP were also tested in sera of 30 healthy children, 25 patients with juvenile onset systemic lupus erythematosus (SLE), and 50 adult patients (30 with RA, 20 with SLE). RESULTS: Positive anti-CCP values were found in sera of two patients with JIA (2%), one with polyarthritis, and one with oligoarthritis. Statistical analysis showed that anti-CCP were not associated with the presence of antinuclear antibodies, raised erythrocyte sedimentation rate, or erosions. In the control groups, none of the patients with juvenile onset SLE and only one of 20 adults with SLE were positive for anti-CCP, but 19/30 (63%) adults with RA showed anti-CCP positivity. CONCLUSIONS: Anti-CCP can be detected in children with JIA, but are less frequently present than in adults with RA.

Martini G, Bacciliero U, Tregnaghi A, Montesco MC, Zulian F. · Department of Pediatrics, University of Padua, Italy. · J Rheumatol. · Pubmed #11469480 No free full text.

Abstract: Temporomandibular joint (TMJ) involvement is quite frequent in juvenile idiopathic arthritis (JIA). We describe a 15-year-old girl with isolated TMJ arthritis presenting as a unique manifestation of JIA, and its successful treatment. She underwent arthroscopic synovectomy followed by intraarticular steroid injection. Early use of synovectomy and intraarticular steroids in TMJ arthritis may reduce pain, improve jaw function, and prevent irreversible deformities.