Objectives To report adverse events (AEs), which led to discontinuation of biologics, in a large cohort of patients with juvenile idiopathic arthritis (JIA) treated with biological therapy (BT). Methods All patients with JIA, non responder or intolerant to DMARDs, treated with BT at the pediatric Rheumatologic Centre of the G Pini Institute (Milan, Italy) from November 1999 to November 2012, were enrolled in an open, single-centre, long-term prospective study. All AEs were recorded on a unique registration form. Results 377 pts (208 etanercept, 89 infliximab, 55 adalimumab, 5 golimumab, 2 certolizumab, 9 abatacept, 7 anakinra, 2 rituximab) were enrolled. Median onset age was 5.8 yrs (mean 6.9, range 0.4-18.0). Median disease duration was 7.5 yrs (mean 9.2, range 0.2-41.4). Median period of follow-up was 5.5 yrs (mean 5.6, range 0-12.7). A total of 220 (58.4%) pts (110 etanercept, 77 infliximab, 25 adalimumab, 5 abatacept, 3 anakinra) failed to respond to or did not tolerate the first therapy and 149 (39.5%) switched to a second one. A total 750 courses of BT (634 anti-TNF, 57 anti-IL-1ra and 59 anti-cells treatments) were administered; 157 (20.9%) AEs occurred and the frequency was 0.09 AEs/patient/year. Infusion reactions led to discontinuation in 38 (24.2%) courses and were the most common AEs in our pts treated with infliximab. The most frequent AEs occurred in pts with JIA on etanercept were important behavioural alterations (depression, anxiety, aggressiveness). One case of hypoglossal paralysis and 2 suspected demielinating disease were reported. New onset of inflammatory bowel disease (9 etanercept and 1 adalimumab) and new onset or flare-up of chronic iridocyclitis (15 etanercept, 1 infliximab, 1 certolizumab) were also reported. Dermatological AEs occorred in 15 (9.6%) courses, most of them were recorded in adalimumab. 9 (6%) cases of injection site reaction were also described. Conclusions In our 13-year, study BT were well tolerated and safe; most of AEs reported were reversible by discontinuation of therapy. In case of active disease it was necessary to switch to another biological agent. Children and young adults affected by JIA should be carefully monitored so as to limit the risk of AEs during BT as much as possible. Disclosure of Interest None Declared

Despite the widely recognized practical importance of anticardiolipin (aCL) ELISA, the reliability of this test has been recently discussed. In order to investigate this area on European scale, we sent to 30 experienced centers a questionnaire focusing on the diagnostic procedures applied to patients with antiphospholipid syndrome (APS) and on the detailed protocols used to perform aCL. Anticardiolipin ELISA was found to be the most frequently performed test in patients with suspected APS, but significant difference was shown among the various protocols. The cross-laboratory multiple examination of ten serum samples evaluated independently by the 24 centers pointed out the difficulty in getting comparable results. Therefore a "consensus" protocol was derived from the aCL methods giving the best performance. The materials and reagents necessary to perform the "consensus" method, including, as putative standards, one IgG and one IgM monoclonal antibody (HCAL and EY2C9) were distributed to 19 Centers. The results of one IgG and one IgM aCL high positive sera measured in serial dilutions were compared. A progressive decrease in the variability of the values obtained for a given sample appeared evident when all the laboratories used the same standard, in their own in-house ELISA and even more in the "consensus" ELISA. Our data show that aCL ELISA standardization is necessary in order to obtain comparable results in different laboratories.

Gastric mucosal histology and function were evaluated in 57 Italian subjects with dermatitis herpetiformis (DH), by means of multiple endoscopic biopsies, gastrin and pepsinogen I (Pg I) serum levels, and parietal cell antibodies (PCA). One hundred and forty-nine patients with nonulcer dyspepsia served as reference population for the prevalence of atrophic gastritis of the body. Seventeen DH patients (30%) and 23 controls (15.4%) showed atrophic gastritis of the body mucosa (p less than 0.05). Nine of the DH patients with atrophic gastritis of the body also had atrophic changes in the antrum. Six patients, all with severe atrophic gastritis, had high gastrin levels and PCA; five of these six also had low Pg I levels. We found an increased prevalence of abnormal indirect function tests among patients with atrophic gastritis is due to the younger age of the patients in our series. Thus, atrophic gastritis can be detected early on a histologic basis, but functional impairment occurs later, as the mucosal damage increases in severity.