Safety of biological agents in paediatric rheumatic diseases: A real-life multicenter retrospective study using the JIRcohorte database.

OBJECTIVE: To analyse and report the incidence of side effects of biological agents in paediatric patients with inflammatory diseases using of real-life follow-up cohort. METHODS: In this international, observational, retrospective, multicentre study of children treated by biological agents and followed in the Juvenile Inflammatory Rheumatism (JIR) cohort (JIRcohorte) network, a Kaplan-Meier method was used to estimate the occurrence of adverse events. A Cox model was constructed to identify independent predictors of adverse events. RESULTS: Overall 813 patients totalling 3439 patients-year (PY) of biological agents were included. The main diagnosis was juvenile idiopathic arthritis (84%). A total of 222 patients (27.3%) had 419 adverse events, representing an incidence rate of 12.2 per 100 PY 95% CI [11.0; 13.4]. The overall incidence rate of serious adverse events was 3.9 per 100 PY 95% CI [3.2; 4.6]. Tocilizumab and infliximab were significantly associated with adverse events and canakinumab with serious adverse events. Univariate and multivariable analysis of adverse events and serious adverse events indicated that patients under biological agents with concomitant immunosuppressive drugs (excluding methotrexate) suffered from more of these events. CONCLUSION: This study suggests an overall an acceptable safety of biologic agents in children with inflammatory rheumatic diseases treated with biological agents. However, the concomitant prescription of immunosuppressive drugs with biological agents represents a substantial risk of adverse events.

Clinical features of childhood granulomatosis with polyangiitis (wegener's granulomatosis).

BACKGROUND: Granulomatosis with polyangiitis (GPA), formerly known as Wegener's granulomatosis (WG), belongs to the group of ANCA-associated necrotizing vasculitides. This study describes the clinical picture of the disease in a large cohort of GPA paediatric patients. Children with age at diagnosis ≤ 18 years, fulfilling the EULAR/PRINTO/PRES GPA/WG classification criteria were extracted from the PRINTO vasculitis database. The clinical signs/symptoms and laboratory features were analysed before or at the time of diagnosis and at least 3 months thereafter and compared with other paediatric and adult case series (>50 patients) derived from the literature. FINDINGS: The 56 children with GPA/WG were predominantly females (68%) and Caucasians (82%) with a median age at disease onset of 11.7 years, and a median delay in diagnosis of 4.2 months. The most frequent organ systems involved before/at the time of diagnosis were ears, nose, throat (91%), constitutional (malaise, fever, weight loss) (89%), respiratory (79%), mucosa and skin (64%), musculoskeletal (59%), and eye (35%), 67% were ANCA-PR3 positive, while haematuria/proteinuria was present in > 50% of the children. In adult series, the frequency of female involvement ranged from 29% to 50% with lower frequencies of constitutional (fever, weight loss), ears, nose, throat (oral/nasal ulceration, otitis/aural discharge), respiratory (tracheal/endobronchial stenosis/obstruction), laboratory involvement and higher frequency of conductive hearing loss than in this paediatric series. CONCLUSIONS: Paediatric patients compared to adults with GPA/WG have similar pattern of clinical manifestations but different frequencies of organ involvement.

CACP syndrome: identification of five novel mutations and of the first case of UPD in the largest European cohort.

Camptodactyly-Arthropathy-Coxa vara-Pericarditis (CACP) syndrome is a rare autosomal recessive disorder caused by mutations in PRG4 gene that encodes for proteoglycan 4, a mucin-like glycoprotein that is the major lubricant for joints and tendon surfaces. The molecular studies reported so far have described the identification of 15 mutations associated with this syndrome and the majority of them were found in families of Arabian origin. Here we report the molecular investigation of the largest European cohort that comprises 13 patients, and allowed the identification of 5 novel mutations and of the first case of CACP syndrome resulting from uniparental disomy of chromosome 1.

Validation of the new paediatric criteria for the diagnosis of familial Mediterranean fever: data from a mixed population of 100 children from the French reference centre for auto-inflammatory disorders.

OBJECTIVE: We aimed to validate the new paediatric criteria for diagnosis of FMF in a mixed population of 100 French patients. METHODS: The study group included 100 FMF children from the French reference centre for auto-inflammatory disorders. A control group of 40 patients with unexplained recurrent fever was reviewed in parallel. Both groups of patients were assessed for both the Tel Hashomer and the new paediatric criteria published by Yalcinkaya et al. RESULTS: Comparison of Tel Hashomer vs Yalcinkaya's criteria in both groups gave a sensitivity of 99 vs 100%, a specificity of 45 vs 50%, a positive predictive value (PPV) of 81.8 vs 83.3% and a negative predictive value (NPV) of 94.7 vs 100%. However, when we used at least three Yalcinkaya's criteria we obtained a sensitivity of 77% and a specificity of 95% with a PPV of 97.3% and an NPV of 62.3%. The number of mutations in the MEFV gene did not modify results for both sets of criteria. CONCLUSION: The new paediatric Turkish criteria did not make a better contribution to FMF diagnosis than the Tel Hashomer criteria in our mixed population of French children while using an appropriate control group. However, if needed, they can be applied using at least three criteria, which slightly decreases their sensitivity but markedly increases their specificity.

EULAR/PRINTO/PRES criteria for Henoch-Schönlein purpura, childhood polyarteritis nodosa, childhood Wegener granulomatosis and childhood Takayasu arteritis: Ankara 2008. Part II: Final classification criteria.

OBJECTIVES: To validate the previously proposed classification criteria for Henoch-Schönlein purpura (HSP), childhood polyarteritis nodosa (c-PAN), c-Wegener granulomatosis (c-WG) and c-Takayasu arteritis (c-TA). METHODS: Step 1: retrospective/prospective web-data collection for children with HSP, c-PAN, c-WG and c-TA with age at diagnosis