Karen Lambot

Phenotypic Characterization of Very Early-onset IBD Due to Mutations in the IL10, IL10 Receptor Alpha or Beta Gene: A Survey of the GENIUS Working Group.

Objective:Early-onset inflammatory bowel disease starting within the first months of life could be due to a particular genetic defect. We set up the GENetically determined ImmUne-mediated enteropathieS (GENIUS) network and collected infants with a proven defect of the IL10 axis for accurate phenotyping of disease presentation and evolution. Design:Ten patients with early-onset inflammatory bowel disease with confirmed mutations in IL10, IL10RA, or IL10RB genes were characterized on clinical, endoscopic–histological, immunobiological, and radiological findings. Functional assays to confirm defective responses to IL10 were performed on peripheral blood mononuclear cells. Results:A functional defect in IL10 signaling was confirmed in all IL10R patients tested. Disease started with severe diarrhea within the first 12 weeks in all patients. All infants showed Crohns disease–like ulcerations limited to the colon with marked perianal inflammation (fissures, abscess, and fistula); disease progression to the small bowel occurred in only 1 patient. Four of the 10 patients had granulomata on histology, and all patients showed Crohns disease–like mesenteric infiltration on imaging. Disease pattern was indistinguishable between IL10R alpha or beta chain or IL10 defects; autoimmunity was not observed. Mutations in IL10 were more frequently associated with bacterial and viral infections. Patients responded partially to treatment with steroids or anti–tumor necrosis factor drugs, whereas hematopoietic stem cell transplantation proved efficacious. Conclusion:The importance of the IL10 pathway within the colonic mucosa is highlighted by the development of severe colitis within a few weeks in infants with mutations in IL10, IL10RA, or IL10RB. Immunosuppression failed to correct the defect in this pathway, which seems to be a key to controlling inflammation in the colon.

Mutation in the SLC29A3 Gene: A New Cause of a Monogenic, Autoinflammatory Condition

Germline mutations in the SLC29A3 gene result in a range of recessive, clinically related syndromes: H syndrome, pigmented hypertrichosis with insulin-dependent diabetes mellitus syndrome, Faisalabad histiocytosis, and sinus histiocytosis with massive lymphadenopathy. The main symptoms of these diseases are hyperpigmentation with hypertrichosis, sensorineural deafness, diabetes, short stature, uveitis, and Rosai-Dorfman like histiocytosis. Here, we report the case of an 11-month-old boy with early-onset, recurrent episodes of unprovoked fever lasting 7 to 10 days and associated with pericardial effusion, abdominal pain, diarrhea, and inflammation. Physical examination revealed hyperpigmentation with hypertrichosis, dysmorphic features, and spleen and liver enlargement. Failure to thrive, sensorineural deafness, retarded psychomotor development, and a Rosai-Dorfman like cheek lesion developed subsequently. The febrile episodes did not respond to tumor necrosis factor α antagonists and interleukin-1. Sequencing of the SLC29A3 gene revealed a homozygous missense mutation c.1088G>A (p.Arg363Gln). These observations suggest that a newly identified mutation in the SLC29A3 gene may be associated with an autoinflammatory disorder. Genetic defects in SLC29A3 should be considered in patients with autoinflammatory manifestations, recurrent febrile attacks, and 1 or more of the symptoms found in the broad spectrum of SLC29A3-related disorders (especially hyperpigmentation with hypertrichosis).

Juvenile overlap myositis: retrospective study about 20 cases

Inflammatory myopathies during childhood are clinically, biologically and pathologically heterogeneous.

A8: Juvenile Idiopathic Arthritis with Dry Synovitis: Clinical and Imaging Aspects in a Cohort of 10 Patients

Dry synovitis is considered to be a rare form of JIA, incompletely understood and following a potentially destructive course. Since its first description only a few reports mention this entity within the spectrum of JIA. We aimed to describe the clinical and radiological manifestations, and the course of dry synovitis and to compare it with classical RF negative polyarticular JIA.

PW03-033 - SLC29A3 mutation: a new autoinflammatory condition

Germline mutations in SLC29A3 result in a range of clinically related, recessive syndromes: H syndrome, pigmented hypertrichosis with insulin-dependent diabetes mellitus (PHID) syndrome, Faisalabad histiocytosis (FHC), and sinus histiocytosis with massive lymphadenopathy (SHML). Main symptoms of these diseases are hyperpigmentation with hypertrichosis, sensorineural deafness, diabetes, short stature, uveitis and “Rosai-Dorfman-like” histiocytosis.

Voluminous Arteriovenous Malformation of a Child's Forearm Treated by Sequential Embolizations: Case Report

An arteriovenous malformation (AVM) is a congenital lesion with high vascular flow resulting from direct connections between arteries and veins. Its treatment is often complex, and most authors recommend a multidisciplinary approach combining surgical and endovascular treatments. We report the case of a 6-month-old boy with a voluminous AVM of the left forearm inducing osteolysis of the radius, with bowing of its diaphysis and subsequent radial head dislocation. Surgical excision of the AVM was not possible, but 2 sequential coil embolizations achieved control of the lesion. After 3.5 years, the AVM was undetectable, and notable improvement was noted both in symptoms and radiographic findings. This case underlines how an AVM can have noteworthy influence on surrounding tissues and shows that embolization alone can achieve a satisfying midterm outcome even when surgery is not possible.

SAT0483 Dry Synovitis: A Unique Entity? A Multicenter Study

Background Dry synovitis (DS) is considered to be a rare form of juvenile idiopathic arthritis (JIA), incompletely understood and following a potentially destructive course. Since its first description only a few reports mention this entity within the spectrum of JIA. Objectives To describe the clinical and radiological manifestations and clinical course of DS and to compare it with classic polyarticular RF negative JIA (c-poly JIA). Methods We performed a retrospective study of 10 patients followed in 3 pediatric rheumatology centers who presented with progressive articular limitations without clinical synovitis and radiologic signs of articular damage. This cohort was compared with a cohort of 35 consecutive patients with classical polyarticular RF negative JIA, seen at the Pediatric Rheumatology Unit of Padua in the period January-June 2012. Clinical, laboratory and imaging (X-rays, MRI) data of both groups were reviewed and compared. Treatment was grouped in 4 categories: no treatment, just corticosteroids (CS), Methotrexate (MTX) + CS, Biological agents (BA) + MTX. Outcome measures included growth, remission state as: clinical remission without medication (CR), clinical remission on medication (CRM), progressive arthropathy with mild functional disability (PA), severe arthropathy with ankylosis and irreversible disability (SA). Results The cohort included 4 male and 6 female, mean (range) age at first manifestation and diagnosis were respectively 4.3 yrs (1.3-8.5) and 7.3 yr (2.8-14). Presenting signs included delayed motor development, progressive articular stiffness and contractures. Little or no pain was present. Clinical examination showed a symmetric and polyarticular involvement without clinical signs of synovitis. CRP was normal in all and ESR>20mm/h in 1/10. In 9/10 patients ANA were absent. Radiological imaging showed osteopenia and/or erosions in all patients. MRI revealed synovial thickening in 9/10 patients; bone edema was variably present and bone erosions were demonstrated in 8/10 patients. Treatments comprised NSAIDs (n=8/10), corticosteroids (n=8/10), methotrexate (n=9/10), biological agents (anti-TNF, IL-RA) (n=6/10). The comparison of DS with c-poly JIA showed that the age at disease onset and at diagnosis were comparable in the two groups. Significant differential features of DS resulted: higher diagnostic delay, increased number of joint involved and joint contractures, lack of swelling/tenderness, prevalent upper limbs involvement, lack of acute phase reactants (ESR, CRP) and no ANA detection. X-ray revealed a significant higher prevalence of osteopenia, erosions and bone edema at MRI in DS. At the last evaluation 77% of patients with c-poly JIA were in CR or CRM while 50% of DS had PA. Growth was significantly impaired in DS (p 0.016). Conclusions Dry Synovitis is actually considered as a subtype of polyarticular JIA. Our study clearly shows that it represents a distinct and unique entity characterized by increased number of joint involved and contractures, prevalent upper limbs involvement, progressive course and lack of acute phase reactants or autoantibodies elevation. The exact nature of DS entity and the possible contribution of metabolic or intrinsic bone disorders into its pathogenesis remain to be determined. Disclosure of Interest None Declared

Juvenile idiopathic arthritis with dry synovitis: clinical and imaging aspects in a cohort of 6 patients

Results The cohort included 2 boys and 4 girls, median (range) age was 9.7yr(3-15). The median (range) age at first manifestation and diagnosis were respectively 4.5yr(1.38.9) and 8.3yr(3-14). Presenting signs comprised delayed motor development and/or progressive articular stiffness. Little or no pain was mentioned. Clinical examination showed a symmetric and polyarticular involvement without obvious clinical signs of synovitis. CRP was normal and ESR<35mm/h. In 5/6 patients ANA was absent. Radiological imaging (wrist and/or pelvis) comprised osteopenia, advanced bone age, irregular bone contours and/or erosions in all patients. MRI revealed synovial thickening in 5/6 patients; bone edema was variably present and bone erosions were demonstrated in 4/6 patients. Treatments comprised NSAIDs(n=5/6), corticosteroids(n=3/6), methotrexate(n=5/6), anti-TNF(n=5/ 6) and resulted in subjective improvement. However articular limitations persisted and imaging showed progressive articular damage.