Sandrine Compeyrot-Lacassagne

The clinical spectrum of 94 patients carrying a single mutated MEFV allele

OBJECTIVE To assess the clinical characteristics of patients living in France and carrying a single MEFV mutation. METHOD A retrospective chart review of patients referred to us for recurrent fevers. Genetic testing: systematic screening of exons 2 and 10 was performed in the MEFV gene. A subset of patients was also investigated for other auto-inflammatory genes. RESULTS We analysed 94 patients (sex ratio:1). Forty-two percent of them were Jews and 17% were Arabs. The median age of onset was 2 years (3 months-47 years). Fever was >39 degrees C in 80% of them, while the duration and frequency of an attack varied (<24 h: 8%; 1-3 days: 56%; >3 days: 36%; >2 months: 15%; 1-2 months: 48%; and <1 month: 37%, respectively). Peritonitis occurred in 97%, pleuritis in 25%, arthralgia in 53%; skin rashes in 20%, aphthosis in 18% and lymphadenopathy in 9%. MEFV mutations were M694V (60%) and M694I (7%). The R92Q TRAPS mutation was retrieved in 3/21 patients tested and the V377I MKD mutation in 1/6. Associated diseases in these patients were periodic fever, aphthosis pharyngitis and adenitis syndrome (4), AS (5), Crohns disease (2) and Castlemans disease (1). CONCLUSION The clinical picture of French heterozygote patients with recurrent fevers resembles that of homozygote patients. Most of them required colchicine treatment.

Adalimumab plus Methotrexate for Uveitis in Juvenile Idiopathic Arthritis

BACKGROUND Adalimumab, a fully human anti–tumor necrosis factor α monoclonal antibody, is effective in the treatment of juvenile idiopathic arthritis (JIA). We tested the efficacy of adalimumab in the treatment of JIA‐associated uveitis. METHODS In this multicenter, double‐blind, randomized, placebo‐controlled trial, we assessed the efficacy and safety of adalimumab in children and adolescents 2 years of age or older who had active JIA‐associated uveitis. Patients who were taking a stable dose of methotrexate were randomly assigned in a 2:1 ratio to receive either adalimumab (at a dose of 20 mg or 40 mg, according to body weight) or placebo, administered subcutaneously every 2 weeks. Patients continued the trial regimen until treatment failure or until 18 months had elapsed. They were followed for up to 2 years after randomization. The primary end point was the time to treatment failure, defined according to a multicomponent intraocular inflammation score that was based on the Standardization of Uveitis Nomenclature criteria. RESULTS The prespecified stopping criteria were met after the enrollment of 90 of 114 patients. We observed 16 treatment failures in 60 patients (27%) in the adalimumab group versus 18 treatment failures in 30 patients (60%) in the placebo group (hazard ratio, 0.25; 95% confidence interval [CI], 0.12 to 0.49; P<0.0001 [the prespecified stopping boundary]). Adverse events were reported more frequently in patients receiving adalimumab than in those receiving placebo (10.07 events per patient‐year [95% CI, 9.26 to 10.89] vs. 6.51 events per patient‐year [95% CI, 5.26 to 7.77]), as were serious adverse events (0.29 events per patient‐year [95% CI, 0.15 to 0.43] vs. 0.19 events per patient‐year [95% CI, 0.00 to 0.40]). CONCLUSIONS Adalimumab therapy controlled inflammation and was associated with a lower rate of treatment failure than placebo among children and adolescents with active JIA‐associated uveitis who were taking a stable dose of methotrexate. Patients who received adalimumab had a much higher incidence of adverse events and serious adverse events than those who received placebo. (Funded by the NIHR Health Technology Assessment Programme and Arthritis Research UK; SYCAMORE EudraCT number, 2010–021141–41.)

Effect of Biologic Treatments on Growth in Children with Juvenile Idiopathic Arthritis

Objective. Growth retardation is a frequent complication of severe juvenile idiopathic arthritis (JIA). Biologic treatments may improve growth velocity by controlling systemic inflammation and reducing corticosteroids. Our goals were to compare growth velocity before and after the onset of biologic therapy and to determine whether the JIA subtype, the use of steroids, the requirement of one or several biologic agents, or the disease activity influenced growth velocity. Methods. We retrospectively analyzed the growth of children with JIA who never received growth hormone treatment, who started biologic treatment before puberty, and who were followed for at least 6 months afterward. Results. We included 100 children (33 boys). Median patient age was 7.1 years (range: 1.6–15.7) at the onset of biologic treatment and 11.0 years (range: 2.3–19.5) at the latest followup. Forty-six patients had received corticosteroid and 34 had received more than 1 biologic agent. Patient median height expressed as SD score (SDS) was 0.31 (range: −2.47 to 5.46) at disease onset, −0.24 (−3.63 to 2.90) at biologic therapy onset (p < 0.0001), and −0.15 (−4.95 to 3.52) at the latest followup (p = 0.171 compared to biologic treatment onset). Patients who required several biologics and systemic patients had a significantly lower growth velocity after the onset of biologic treatment. At the latest followup, 18% of our study group had low growth velocities and 19% were below −2SD or shorter than genetically programmed. Conclusion. In a subset of patients, particularly systemic JIA patients and patients who required more than 1 biologic, biologic therapy may be insufficient to restore normal growth velocity.

Functional status in severe juvenile idiopathic arthritis in the biologic treatment era: an assessment in a French paediatric rheumatology referral centre

OBJECTIVES To investigate the functional status of difficult-to-treat JIA patients, including patients receiving biotherapies, and to correlate functional status to disease activity. METHODS All JIA patients consecutively evaluated in a paediatric rheumatology referral centre (November 2008 to March 2009) were enrolled in an observational cross-sectional study. The Childhood HAQ (CHAQ), physicians assessment of overall disease activity, parents assessment of well-being and pain, and active and limited joint numbers were measured. RESULTS We enrolled 95 patients [27% systemic, 29% polyarticular, 22% enthesitis-related arthritis (ERA) and 23% oligoarticular JIA]. Median disease duration was 3.5 years. Treatment included NSAIDs (56%), MTX (23%), CSs (21%) and biologics (45%). Of all patients, 31 and 56%, respectively, had inactive and minimally active disease. The median CHAQ score was 0.375 (range 0-3). Most patients had no or mild functional disability (61%), impaired well-being (63%) or pain (55%); 10% reported severely impaired function and well-being, 19% severe pain. ERA patients reported worse well-being and pain. CHAQ scores correlated with disease activity. Long-lasting disease and biologic treatment were associated with better well-being and pain scores. CONCLUSION Despite the high proportion of severe JIA patients in this cohort, CHAQ values are within the lower range of recent reports, probably related to new therapeutic approaches. Impaired function and well-being remain a challenge for at least 10% of the patients. Impaired well-being and pain in ERA patients require further study. The strong correlation between functional status and well-being underlines the importance of improving function to optimize quality of life.

Juvenile arthritis disease activity score is a better reflector of active disease than the disease activity score 28 in adults with polyarticular juvenile idiopathic arthritis

A considerable proportion of children with polyarticular juvenile idiopathic arthritis (polyJIA) experience active disease into adulthood.1 However, there is no validated disease activity measure for adults with polyJIA, and they are often assessed using the disease activity score 28 (DAS28). DAS28 is validated in adults with rheumatoid arthritis (RA), and determines qualification for biological drugs in the UK and other countries.2 ,3 In contrast to the juvenile arthritis disease activity score (JADAS),4 DAS28 does not fully evaluate the pattern of joint involvement often observed in polyJIA. In this study, we compared DAS28 with JADAS-10 in adolescents and adults with polyJIA. Tender and swollen joint counts out of 28, active joint count of all joints up to a maximum of 10, patient/parent and physician global assessment visual analogue scales were collected from clinics in patients aged ≥10 years with polyJIA (International League of Associations for Rheumatology classification criteria for rheumatoid factor-negative (RhF-ve) or rheumatoid factor-positive (RhF+ve) polyJIA). Erythrocyte sedimentation rate (ESR) values were taken within 30 days before or after assessment. When unavailable, values were taken within 3 months before or after, provided the patient remained stable between the ESR test and assessment. When unavailable within these time periods, patients were excluded from …

Infantile-onset LMNA-associated Muscular Dystrophy Mimicking Juvenile Idiopathic Inflammatory Myopathy.

To the Editor: Juvenile idiopathic inflammatory myopathy (JIIM) refers to a group of rare chronic autoimmune conditions. Juvenile dermatomyositis (JDM) is the most common JIIM. The hallmarks of JDM are characteristic cutaneous features and proximal muscle weakness; however, adermatitic forms have been described. Polymyositis presents with both proximal and distal muscle weakness, muscle atrophy, and similar degrees of dysphagia, arthritis, and contractures1. Although magnetic resonance imaging (MRI) is widely used, muscle biopsy remains a critical tool in the diagnosis of JIIM, especially in atypical cases1. Recently, LMNA -associated congenital muscular dystrophy (LMNA-CMD) has been reported as a novel and severe form of laminopathy with secondary inflammatory changes mimicking inflammatory myopathies2,3. Mutations in the LMNA gene encoding lamin A/C are responsible for multiple disease phenotypes4. Some of them may present early in life as a congenital muscular dystrophy2,3. ### Patient We report the case of a 26-month-old girl, first child of non-consanguineous parents, who was referred to our department based on a history of progressive muscle weakness with raised creatine kinase (CK) and a muscle biopsy showing marked inflammation. There was no family history of neuromuscular or autoimmune diseases. She was born by normal uncomplicated delivery; no reduced fetal movements were described by the mother during pregnancy. By 1 year of age, she was … Address correspondence to Dr. E. Moraitis, Rheumatology Department, Great Ormond Street Hospital for Children, Great Ormond Street, London, WC1N 3JH, UK. E-mail: elena.moraitis.13{at}ucl.ac.uk

SAT0518 Treatment Pathway of Patients with Juvenile Idiopathic Arthritis (JIA)-Associated Uveitis Requiring Systemic Immunosuppression

Background JIA-associated uveitis is an insidious and often asymptomatic complication of JIA. Up to 30% of patients with JIA will develop uveitis depending of their diseases subgroup, the extended oligoarticular JIA being the most often affected group. There is also evidence of an association with positive ANA. More than 50% of patients with JIA-associated uveitis will develop complications including cataract and glaucoma. Although the risk of blindness is low, the risk of functional impairment is much higher. Increasing uveitis activity was associated with increased risk of vision loss. Use of immunosuppressive drugs was associated with reduced risk of vision loss. Control of inflammation and use of immunosuppression may be critical aspects in improving outcome although little evidence is yet available. Objectives To identify the proportion of patients with JIA-associated uveitis who discontinued Methotrexate (MTX) due to remission To identify the proportion of patients with JIA-associated uveitis who require an anti-TNF biologic agent for the management of uveitis Methods We conducted a retrospective review of the clinical notes of patients diagnosed with JIA-associated uveitis between 1993 and 2009. We excluded the patients who did not require systemic treatment and those with incomplete record. We identified a total of 81 patients. Results MTX was stopped due to remission in 18 patients (22.2%) but 3 patients were started on an anti-TNF. Therefore, only 15 patients (18.5%) could stop MTX due to remission without using systemic medication. MTX was stopped in 13 patients (16.0%) due to side effect or non-compliance. In that group, six patients were switched to other immunosuppressive drugs including anti-TNF in four patients. MTX was continued in the remaining 50 patients (61.7%). Biologics and Cyclosporin A were added as in 11 and 4 patients respectively for further disease control. For those on additional Cyclosporin A, 3/4 patients were switched to an anti-TNF later. In the group of patients remaining on MTX, 14/50 patients (28%) required the addition of an anti-TNF for the control of their uveitis. Some of the patients in the MTX group have been on this medication for over 10 years. In summary, 21/81 patients (25.9%) have been on an anti-TNF agent and 14/21 patients have been receiving a biologic along with MTX. At the last follow up, 57/81 patients (70.7%) required long term systemic immunosuppression mostly MTX (87.7%). 21 (36.8%) out of the 57 patients were started on anti-TNF either with MTX or alone. Conclusions Over 2/3 of the patients have to remain on long-term systemic immunosuppression (mostly MTX) for the management of their uveitis. About 1/3 of them require long-term anti-TNF therapy either alone or along with MTX. Although this has led to a better visual functional outcome, it is associated with potential side-effects which need monitoring and an increased cost of management. Disclosure of Interest None declared

P03-018 - Diversity in presenting manifestations of AUTOINFL

The autoinflammatory diseases (AID) include monogenic and polygenic disorders characterized by primary dysfunction of the innate immune system.

Diversity in clinical manifestations of autoinflammatory syndromes

Results Fifty six patients were included: 17 CAPS, 4 TRAPS, 5 HIDS, 18 FMF, 6 CRMO, 2 SAPHO and 4 Behcet. The median follow-up period was 2 years (0-14 years). The male/female ratio was 20/36. The median age was 2.5 years at disease onset and 4 years at diagnosis. Family history was positive in 34% of patients. Clinical manifestations included fever (79%), mucocutaneous (61%), musculoskeletal (77%), ocular (34%), cardiorespiratory (12%), gastrointestinal (62%), neurological (41%) and genitourinary (2%) findings, lymphadenopathy with/or hepatosplenomegaly (16%) and growth impairment (27%). Seven patients presented severe manifestations: neonatal peritonitis (1 CAPS), pancreatitis (1 TRAPS), acute glomerulonephritis (1 FMF), complicated Henoch-Schonlein purpura (1 FMF), peritoneal adhesions with intestinal occlusion (1 FMF), periorbital pain (1 CRMO), and cerebral thrombosis (1 Behcet). One mutation was found in 93% of CAPS, and in all TRAPS patients. Two mutations were present in 11% of FMF, and in all HIDS patients. 43% of patients received colchicine, 23% steroids, and 54% biologics (Anakinra, Canakinumab, Etanercept). 57% of patients were in complete and 41% in partial remission.