To obtain international consensus around processes that support the delivery of high‐quality care to patients with childhood‐onset systemic lupus erythematosus (SLE) based on current recommendations and scientific evidence.

Neuropsychiatric involvement is one of the most common features of childhood-onset systemic lupus erythematosus (cSLE) occurring in 20 to 95% of patients. The large variation in frequency of neuropsychiatric manifestations reported in cSLE is the result of differing case definitions and the methods used for evaluation. The majority of patients with neuropsychiatric involvement have the initial signs and symptoms early in the course of the disease and approximately 25% develop initial neuropsychiatric manifestations more than 2 years after disease onset. There have been few comprehensive studies evaluating neuropsychiatric disease in cSLE. In general, central nervous system involvement appears to be more severe in children than in adults and cSLE is associated with higher accrual of permanent organ damage. The most common neuropsychiatric manifestation in cSLE is headache occurring in approximately 50% of patients. Neurocognitive deficits in cSLE ranges from concentration difficulties, a decrease in school performance to frank confusion and coma. Since there are no validated clinical or research neuropsychological testing for children, it is particularly difficult to determine subtle neurocognitive impairment in cSLE. Cerebrovascular disease occurs in up to 30% of patients with neuropsychiatric involvement and is usually associated with the presence of antiphospholipid antibodies. Antiphospholipid antibodies have been associated also with other neuropsychiatric manifestations, in particular movement disorders (chorea), seizures, psychosis and transverse myelopathy. These latter manifestations are likely the result of a nonthrombotic, immune-mediated mechanism rather than thrombosis. Involvement of peripheral nervous system has been infrequently described in cSLE, mainly as isolated case reports only. The diagnosis of neuropsychiatric involvement in cSLE is often difficult, as both focal and diffuse manifestations may occur and there is no gold standard for diagnosis. A high index of clinical suspicion, in addition to laboratory and neuroimaging findings may support the diagnosis. It is important to exclude other causes such as infection, hypertension or metabolic abnormalities associated with neuropsychiatric signs and symptoms. The management of patients with neuropsychiatric cSLE requires interdisciplinary approach and includes symptomatic and immunosuppressive medications. In patients with severe neuropsychiatric involvement a combination therapy with high-dose steroids and cyclophosphamide is usually required. Psychotropic medications and supportive non-pharmacological approaches are frequently required in patients with psychiatric disorders and cognitive dysfunction. In the future, it is expected that novel biomarkers and advanced neuroimaging modalities will provide better understanding of the underlying mechanisms of neuropsychiatric involvement in cSLE and help guide therapeutic decisions. Disclosure of Interest None Declared

Background Anti drug antibodies are known to alter drug pharmacokinetics, decrease drug efficacy and in rare cases they may also lead to life-threatening anaphylactic or anaphylactoid reactions. Infliximab is a chimeric monoclonal antibody that is due to its variable domains of murine origin often immunogenic for its recipients. Previously, we reported that antibodies to infliximab (ATI) developed in nearly 43% of the pediatric patients with rheumatic diseases that were treated with infliximab. The development of ATI was in all cases associated with decreased infliximab serum trough levels and decreased drug efficacy (Kosmač et al., 2011). Objectives In the present study we analyzed the isotypes (IgG, IgM, IgA and IgE) and in the case of IgG antibodies also the subtypes (IgG1, IgG2, IgG3 and IgG4) of ATI-positive serum samples from pediatric patients treated with infliximab. Methods We compared the isotype-specific binding assay with the more common double antigen bridging assay and used both to analyze 121 serum samples from 21 pediatric patients treated with infliximab. In the 36 serum samples that tested positive for ATI in the isotype-specific binding assay we also used this assay to subsequently determine the isotypes and IgG subtypes of the detected antibodies. Results The predominant ATI isotype was IgG (median [IQR] =60.5% [65.4%]), followed by IgA (35.4% [65.5%]), IgE (0.8% [0.9%]) and IgM (bellow detection). More specifically, the two most represented IgG subtypes were IgG1 and IgG3 (27.9% [52.9%] and 20.4% [38.6%] of total IgG, respectively). However, in the majority of sera tested several different isotypes and subtypes were observed simultaneously and in the cases where high absolute ATI values were observed there was a high proportion of IgG4 (30.6% [13.8%]). Conclusions As expected for T-dependent protein antigens, ATI were predominantly of the IgG isotype. There was a low prevalence of IgE antibodies, also in the cases where patients experienced infusion-related reactions, arguing against the classical type I hypersensitivity. After IgG, the second most prominent anti-infliximab isotype were IgA antibodies, which are generally not regarded as a clinically significant antibody isotype, but may along with IgG4 play an immunoprotective role in the chronic exposure to a specific antigen. Additionally, we found that the isotype-specific binding assay was faster, more sensitive and less influenced by residual drug interference than the more common bridging assay. It is however, more prone to false positive results and should therefore be employed in the screening phase of ADA determination. References Kosmač, M., Avčin, T., Toplak, N., Simonini, G., Cimaz, R. and Čurin Šerbec, V., 2011. Exploring the binding sites of anti-infliximab antibodies in pediatric patients with rheumatic diseases treated with infliximab. Pediatric Research, 69(3), pp. 243-248. Disclosure of Interest None Declared

Approximately 20% of patients withy systemic lupus erythematosus (SLE) have disease which begins in childhood. Several series have reported that childhood-onset SLE (cSLE) is often more severe than adult disease with more pronounced clinical, immunologic and serologic abnormalities. In particular, renal and central nervous system (CNS) involvement tend to be more severe in pediatric than in adult patients. The morbidity and mortality associated with SLE result from a combination of severe organ damage from disease, infection or side effects and complications of treatment. Since neither disease activity nor disease damage in SLE can be measured directly with any clinical sign or laboratory value, a number of disease indices have been developed that allow standardized comparison of SLE cohorts. Disease activity indices including SLEDAI, SLAM, BILAG and ECLAM have been validated in cSLE and none appears superior. The SLICC damage index was developed to measure permanent disease damage in adults with SLE and was subsequently validated in cSLE. It has been suggested that pediatric version should include additional domains addressing pediatric specific issues such as growth failure and delayed puberty, but both indices are reversible and they do not fulfil the definition of nonreversible organ damage. Several predictors (risk factors) have been linked with poor prognosis in cSLE. Using the SLICC-DI scoring system for damage, it has been demonstrated that renal and/or CNS disease represent major determinants of morbidity and mortality in cSLE. Diffuse proliferative glomerulonephritis is most consistently linked with a poor prognosis if associated with hypertension. Other suggested risk factors associated with poor prognosis in cSLE include acute thrombocytopenia, young age at diagnosis, male sex and nonwhite (black, Asian and Hispanic) ethnicity. The presence of antiphospholipid antibodies may predispose to disease damage by increasing the risk for recurrent venous thrombosis, stroke and thrombocytopenia. Similar to previous adult studies, it has been shown in cSLE that cumulative disease activity over time results in increased damage, and early introduction of therapy with immunosuppressive drugs might improve the outcome by preventing permanent damage. The exact impact of corticosteroid therapy on increased disease damage is still controversial, but patients may benefit from judicious use of corticosteroid with refined tapering schedules and early introduction of steroid-sparing drugs. It has been also demonstrated that frequent occurrence of severe, major disease flares requiring intravenous cyclophosphamide treatment represent a risk factor for damage, but not mild or moderate flares. Disclosure of Interest None Declared