A. Duquesne

Clinical outcome in children with chronic recurrent multifocal osteomyelitis

OBJECTIVE To determine the clinical outcome of children with chronic recurrent multifocal osteomyelitis (CRMO). METHODS We retrospectively reviewed clinical, biological and radiological data of children with CRMO at five French paediatric centres. Outcome data were obtained through review of hospital charts and questionnaires sent to all patients to assess disease activity and educational and vocational achievement. RESULTS Forty patients were assessed (34 females and 6 males) with a median age at diagnosis of 11.5 yrs (range 2-17). Median number of initial bony lesions was 2 at onset, and 3.5 over disease course. Median time since diagnosis was 3.5 yrs (range 0.5-15) and median duration of active disease 2.7 yrs (range 0.5-13.5). Nine (22.5%) patients had psychological or physical sequelae. Twenty-nine children (72.5%) responded to the questionnaire. Twenty-six had no physical disability as judged by the HAQ 0-1, two had moderate disability (HAQ: 1-2) and one had severe disability (HAQ: 2-3). Seventeen patients (58.6%) had active disease at follow-up (after 6 months to 15 yrs since diagnosis) and continued to have pain (median value of visual analogue scale: 10/100). CRMO had interfered with patients education in two cases. CONCLUSIONS Clinical outcome of children with CRMO is generally good, but a sizeable proportion of patients have active disease at follow-up, and a minority of patients can have a severe and prolonged disease course despite intensive treatments. Further studies are required to determine predictive factors for severe disease.

A preliminary score for the assessment of disease activity in hereditary recurrent fevers: results from the AIDAI (Auto-Inflammatory Diseases Activity Index) Consensus Conference

Background The systemic autoinflammatory disorders (SAID) share many clinical manifestations, albeit with variable patterns, intensity and frequency. A common definition of disease activity would be rational and useful in the management of these lifelong diseases. Moreover, standardised disease activity scores are required for the assessment of new therapies in constant development. The aim of this study was to develop preliminary activity scores for familial Mediterranean fever, mevalonate kinase deficiency, tumour necrosis factor receptor-1-associated periodic syndrome and cryopyrin-associated periodic syndromes (CAPS). Methods The study was conducted using two well-recognised consensus formation methods: the Delphi technique and the nominal group technique. The results from a two-step survey and data from parent/patient interviews were used as preliminary data to develop the agenda for a consensus conference to build a provisional scoring system. Results 24 of 65 experts in SAID from 20 countries answered the web questionnaire and 16 attended the consensus conference. There was consensus agreement to develop separate activity scores for each disease but with a common format based on patient diaries. Fever and disease-specific clinical variables were scored according to their severity. A final score was generated by summing the score of all the variables divided by the number of days over which the diary was completed. Scores varied from 0 to 16 (0–13 in CAPS). These scores were developed for the purpose of clinical studies but could be used in clinical practice. Conclusion Using widely recognised consensus formation techniques, preliminary scores were obtained to measure disease activity in four main SAID. Further prospective validation study of this instrument will follow.

Pediatric-Onset Relapsing Polychondritis: Case Series and Systematic Review

OBJECTIVES To study the pediatric presentation and evolution of relapsing polychondritis (RP), a rare inflammatory disease characterized by recurrent inflammation of cartilage. STUDY DESIGN We retrospectively collected data from 10 patients observed in 3 French hospitals for relapsing polychondritis, with an age at onset <18 years. We also analyzed 37 cases of pediatric-onset RP from a systematic review. RESULTS The mean age at first symptoms was 8.6 years, and the sex ratio was 6 male patients and 4 female patients. Children came to medical attention with joint pain, ocular inflammation, and chondritis. Outcomes included severe visual impairment, chronic destructive chondritis, and 1 death caused by aortic dilatation. Treatment mainly consisted of non-steroidal-anti-inflammatory drugs, corticosteroids, and immunosuppressants. Growth was normal in 7 examined patients. Systematic literature review also suggested a high number of tracheostomy in pediatric cases, but this was not confirmed in our series. CONCLUSION RP in childhood shares the main clinical features of its adult counterpart, including destructive chondritis and systemic symptoms, but unlike adults, children frequently have a family history of autoimmunity and infrequently have other associated autoimmune diseases. RP can be fatal; close screening for complications is mandatory. Growth does not appear to be impaired by cartilage inflammation.

Validation of the French version of the Childhood Health Assessment Questionnaire (CHAQ) in juvenile idiopathic arthritis

OBJECTIVES To translate, cross-culturally adapt, and validate the functional disability tool Childhood Health Assessment Questionnaire (CHAQ), a variant of the Health Assessment Questionnaire (HAQ), in children with juvenile idiopathic arthritis (JIA). CHILDREN AND METHODS The disability index is the mean of the scores on the eight domains of the CHAQ and can range from 0 (no disability) to 3 (maximum disability). The CHAQ was first translated into French and adapted, then validated in a multicenter cross-sectional study in 306 children with JIA (systemic onset, 23%; polyarticular onset, 22%; extended oligoarticular subtype, 25%; and persistent oligoarticular subtype, 30%). RESULTS Overall CHAQ scores discriminated between the four JIA subtypes (systemic: 1.1 +/- 0.9; polyarticular: 0.8 +/- 0.7, extended oligoarticular 0.8 +/- 0.7, and persistent oligoarticular: 0.4 +/- 0.5 [P < 0.0001]). Reproducibility evaluated by test-retest at a 7-day interval was excellent (intraclass coefficient, 0.91), as was agreement between the Parents and Childrens versions of the questionnaire (intraclass coefficient, 0.89). Significant correlations were found between the overall CHAO score and variables reflecting disease severity (joint counts, physicians and parents global assessments, and erythrocyte sedimentation rate), indicating excellent convergent validity of the tool. CONCLUSION The French version of the CHAQ displays good psychometric characteristics, although its sensitivity to change remains to be established. The French version of the CHAO should prove useful in international studies and can be expected to be helpful for monitoring individual patients with JIA.

Efficacy, safety and effect on gene expression profiling of anakinra in systemic-onset juvenile idiopathic arthritis: final results of a randomised, double-blind, placebo-controlled trial (ANAJIS)

Open Access Poster presentation Efficacy, safety and effect on gene expression profiling of anakinra in systemic-onset juvenile idiopathic arthritis: final results of a randomised, double-blind, placebo-controlled trial (ANAJIS) P Quartier*1, F Allantaz2, R Cimaz3, P Pillet4, O Richer4, M Desjonqueres3, A Duquesne3, C Messiaen1, C Bardin5, X Bossuyit6, A Boutten7, J Bienvenu8, V Menoni1, S Sotou-Bere1, B Neven1, N Mahloui1, A Mogenet1, B Kassai3, D Chaussabel2, JM Treluyer1, JL Bresson1, P Landais1 and V Pascual2

Tocilizumab in the treatment of mixed connective tissue disease and overlap syndrome in children

Arthritis is one of the main manifestations of mixed connective tissue disease (MCTD) and overlap syndrome in children and can be responsible for functional disability. We report on 2 children with arthritis that were dramatically improved by a treatment with interleukin-6 (IL-6) blockers in the context of connective tissue disease. However, in both cases, other systemic autoimmune symptoms were not modified by the treatment and autoantibodies tend to increase, suggesting a differential effect of IL-6 inhibition on articular inflammation and systemic autoimmunity.

Musculoskeletal Symptoms in Patients With Cryopyrin-Associated Periodic Syndromes: A Large Database Study

To determine the type and frequency of musculoskeletal symptoms at onset and during followup of cryopyrin‐associated periodic syndromes (CAPS).

Familial Mediterranean fever mutations are hypermorphic mutations that specifically decrease the activation threshold of the Pyrin inflammasome

Objectives FMF is the most frequent autoinflammatory disease and is associated in most patients with bi-allelic MEFV mutations. MEFV encodes Pyrin, an inflammasome sensor activated following RhoGTPase inhibition. The functional consequences of MEFV mutations on the ability of Pyrin variants to act as inflammasome sensors are largely unknown. The aim of this study was to assess whether MEFV mutations affect the ability of Pyrin to detect RhoGTPase inhibition and other inflammasome stimuli. Methods IL-1β and IL-18 released by monocytes from healthy donors (HDs) and FMF patients were measured upon specific engagement of the Pyrin, NLRP3 and NLRC4 inflammasomes. Cell death kinetics following Pyrin activation was monitored in real time. Results Monocytes from FMF patients secreted significantly more IL-1β and IL-18 and died significantly faster than HD monocytes in response to low concentrations of Clostridium difficile toxin B (TcdB), a Pyrin-activating stimulus. Monocytes from patients bearing two MEFV exon 10 pathogenic variants displayed an increased Pyrin inflammasome response compared with monocytes from patients with a single exon 10 pathogenic variant indicating a gene-dosage effect. Using a short priming step, the response of monocytes from FMF patients to NLRP3- and NLRC4-activating stimuli was normal indicating that MEFV mutations trigger a specific hypersensitivity of monocytes to low doses of a Pyrin-engaging stimulus. Conclusion Contrary to the NLRP3 mutations described in cryopyrin-associated periodic syndrome, FMF-associated MEFV mutations do not lead to a constitutive activation of Pyrin. Rather, FMF-associated mutations are hypermorphic mutations that specifically decrease the activation threshold of the Pyrin inflammasome without affecting other canonical inflammasomes.

Creation of a cohort of French patients with chronic recurrent multifocal osteitis : preliminary results

Chronic recurrent multifocal osteomyelitis (CRMO), also known as chronic nonbacterial osteomyelitis, is an orphan disease that manifests as recurrent flares of inflammatory bone pain with or without a fever. Its frequency seems to be underestimated and it often leads to consequential residual impairments.

CL172 - Ostéoporose Idiopathique Juvénile : présentation d’une série de 24 patients

Introduction L’osteoporose idiopathique juvenile (OIJ) est une pathologie rare. L’objectif de ce travail etait d’en preciser la presentation clinique et l’evolution notamment depuis l’introduction du traitement par bisphosphonates. Patients et Methodes Nous avons mene une etude retrospective multicentrique incluant 24 enfants. La remission a ete definie par l’absence de douleur, de fractures et l’amelioration de la densite minerale osseuse (DMO) apres 3 ans de traitement. Resultats La mediane d’âge etait de 12 ans, 6/14 enfants avaient des antecedents familiaux d’osteoporose. Le motif de consultation etait la demineralisation osseuse, les fractures repetees, les douleurs dues aux tassements vertebraux. Dix/24 patients ont ete traites par bisphosphonates. Le nombre de patients en remission etait plus important dans le groupe traite par bisphosphonates (75 % vs 35 %) mais non significatif, et le gain de z-score etait plus important dans le groupe traite (+1,6DS vs +0,18DS). Cinq enfants gardaient des sequelles importantes quelque soit le traitement. Conclusion Les donnees de notre etude laissent suspecter une predisposition genetique dans l’OIJ. L’utilisation des bisphosphonates doit etre prudente, mais discutee en cas d’atteinte severe avec baisse importante de la DMO.