Chantal Job-Deslandre

Long-term outcome and prognosis in oligoarticular-onset juvenile idiopathic arthritis.

OBJECTIVEnTo describe the long-term outcome and determine predictors of severity among patients with oligoarticular-onset juvenile idiopathic arthritis (JIA).nnnMETHODSnIn a longitudinal study, 207 patients with oligoarticular-onset JIA who were referred between 1988 and 1998 were evaluated. At disease onset, selected clinical and laboratory data were collected as independent variables. A polyarticular disease course, joint erosion, uveitis, and remission were assessed as dependent variables. Longitudinal analyses were performed with the Kaplan-Meier method, and multivariate analysis with the Cox model.nnnRESULTSnAfter 6 years of followup, the probability of a polyarticular course of disease was 50%, joint erosion was 35%, uveitis was 30%, and remission was 23% in these patients. Joint erosion was strongly associated with a polyarticular course. A high erythrocyte sedimentation rate (ESR) as well as involvement of more than 1 joint or involvement of an upper limb at disease onset were predictors of disease extension. A high ESR was also a strong predictor of a destructive course, and a family history of psoriasis was predictive of uveitis occurrence. No predictive factor for remission could be identified.nnnCONCLUSIONnOligoarticular-onset JIA is a severe disease with frequent complications. Factors predictive of severity in oligoarticular-onset JIA were identified. This could allow early identification of high-risk patient subgroups, warranting a more aggressive therapeutic approach.

Tartrate-resistant acid phosphatase deficiency causes a bone dysplasia with autoimmunity and a type I interferon expression signature

We studied ten individuals from eight families showing features consistent with the immuno-osseous dysplasia spondyloenchondrodysplasia. Of particular note was the diverse spectrum of autoimmune phenotypes observed in these individuals (cases), including systemic lupus erythematosus, Sjögrens syndrome, hemolytic anemia, thrombocytopenia, hypothyroidism, inflammatory myositis, Raynauds disease and vitiligo. Haplotype data indicated the disease gene to be on chromosome 19p13, and linkage analysis yielded a combined multipoint log10 odds (LOD) score of 3.6. Sequencing of ACP5, encoding tartrate-resistant acid phosphatase, identified biallelic mutations in each of the cases studied, and in vivo testing confirmed a loss of expressed protein. All eight cases assayed showed elevated serum interferon alpha activity, and gene expression profiling in whole blood defined a type I interferon signature. Our findings reveal a previously unrecognized link between tartrate-resistant acid phosphatase activity and interferon metabolism and highlight the importance of type I interferon in the genesis of autoimmunity.

Les maladies ossifiantes d’origine génétique

Resume Ces affections genetiquement determinees et cliniquement bien identifiees comportent la survenue progressive d’ossification de siege ectopique. La fibrodysplasie ossifiante progressive (FOP) comporte une ossification a point de depart musculaire pouvant conduire a la creation d’un veritable deuxieme squelette. Sa transmission semble de type autosomique dominante mais les cas sporadiques sont plus frequents. Elle comporte egalement des anomalies squelettiques morphologiques caracteristiques au niveau du pied et du rachis cervical. Le mecanisme physiopathogenique semble faire intervenir une anomalie au niveau de la Bone Morphogenic Proteine 4. L’anomalie genetique reste discutee : une mutation situee sur le chromosome 17 au niveau du gene Noggin, inhibiteur de BMP4, ou mutation situee sur le chromosome 4 dans une zone impliquee dans la voie de signalisation d’une BMP et dans le developpement squelettique. La deuxieme maladie ossifiante d’origine genetique est de description plus recente : l’hyperplasie ossifiante progressive (HOP), n’a ete reconnue que recemment a partir de formes atypiques de FOP. Une etude familiale a permis de rapprocher l’HOP de l’osteodystrophie hereditaire d’Albright et d’affirmer que l’HOP comportait egalement une anomalie au niveau de la sous-unite α de la proteine G. Cette maladie est egalement de transmission autosomique dominante. Les ossifications contrairement a la FOP sont a point de depart au niveau des fascias. Ces deux maladies different par les donnees d’imagerie et egalement par le mecanisme physiopathogenique puisque dans le cas de la FOP c’est la transformation des fibroblastes en cellule productrice d’os avec ossification type enchondrale et dans l’HOP une transformation des cellules adipeuses en cellules productrices d’os avec une ossification de type membraneuse. Actuellement les mecanismes de ces processus d’ossification ne sont que partiellement elucides et aucune therapeutique autre que symptomatique n’est disponible.

Treatment of active rheumatoid arthritis: comparison of patients younger vs older than 75 years (CORPUS cohort)

ABSTRACT Objectives: Little information is available on the characteristics of elderly patients starting TNFα antagonist treatment for rheumatoid arthritis (RA). The objective of this work was to compare prescription patterns in RA patients younger vs. older than 75 years. Methods: Biologic-naive patients with active RA (DAS28 > 3.2) despite first-line therapy were included between 2007 and 2009 in the prospective, multicentre, longitudinal, observational, population-based CORPUS-RA cohort. TNFα antagonist users were defined as having received at least one TNFα antagonist during the first study year. The groups < 75 years and ≥ 75 years were compared regarding comorbidities, inflammation (CRP and ESR), disease activity (DAS28), disability (HAQ-DI), number of physician visits, and treatment. To verify the impact of the cut off, we also compared patients aged 70 years or more to patients younger than 70 years. Results: Of 543 RA patients, 382 had complete one-year follow-up data, including 114 TNFα antagonist users, 3 (6%) among the 49 patients aged 75 years or over and 111 (32%) of the 333 patients younger than 75 years (p < 0.01). Disease activity in the two age groups was similar at inclusion and after one year. Comorbidities and a history of auto-immunity were more common in the older group. Compared to their younger counterparts, the older patients received glucocorticoids more often (p = 0.003) and synthetic disease-modifying anti-rheumatic drugs less often (p = 0.01). Conclusion: TNFα antagonists are used less often and glucocorticoids more often in elderly patients with active RA compared to their younger counterparts. The fact that this study was performed in 2007–9 is a limitation in terms of relevance to today’s patients and further studies should be conducted in new cohorts of active RA.

Traitement par lavage articulaire des atteintes récidivantes du genou au cours des arthrites juvéniles idiopathiques (AJI)

Objective. – To retrospectively evaluate the benefits of knee joint lavage with intraarticular glucocorticoid injection in patients who have juvenile idiopathic arthritis with knee involvement unresponsive to repeated intraarticular glucocorticoid injections. n nPatients. – Seventeen knees in 10 children (eight girls and two boys) were treated from 1997 to 2000. Mean age was 14 years 9 months and the mean disease duration was 7.2 years. The diagnoses were juvenile oligoarthritis (n = 6, including 2 with extended disease), systemic arthritis (n = 2), juvenile spondyloarthropathy (n = 1), and juvenile dermatomyositis (n = 1). Repeated intraarticular triamcinolone hexacetonide injections had been performed in all the patients, the mean number of injections being 2.2/patient within the last 30 months. Plain radiographs were normal in six of the eight patients. Mean erythrocyte sedimentation rate was 21.7 mm/h and mean C-reactive protein level was 20.6 mg/l. Joint fluid was obtained from 10 knees and had a mean cell count of 12,660/mm3. Second-line therapy was with methotrexate alone or combined with cyclosporine or azathioprine. Oral glucocorticoids and/or nonsteroidal antiinflammatory drugs were used for symptom relief. n nTreatment procedure. – Lavage was performed under strict aseptic conditions with simple analgesia, on a day-hospital basis. After aspiration of the joint, lavage was performed with saline, and a delayed-action glucocorticoid was injected. The knee joint was immobilized in the extended position for 48 h. Efficacy criteria were the presence of effusion, presence of pain, and the presence of a systemic treatment-sparing effect. n nResults. – Freedom from effusion and pain was noted in all 17 knees after 1 month, in eight (47%) knees after 6 months, and in seven (41%) knees after 12 months. The patients with the long lasting improvements had systemic polyarthritis. After joint lavage, second-line treatment was reduced in two patients and the oral glucocorticoid therapy was stopped in the other two. None of the variables studied (age, sex, disease duration, inflammatory syndrome, or joint fluid cytology) predicted a good response. No adverse effects were recorded. n nConclusion. – These preliminary results show that joint lavage with glucocorticoid injection is safe in children. The improvements were modest, but the patients had a history of arthritis refractory to multiple triamcinolone hexacetonide injections. Thus, joint lavage may have a place in the treatment pyramid just before synovectomy.