@article {10549, title = {ADA2 deficiency (DADA2) as an unrecognised cause of early onset polyarteritis nodosa and stroke: a multicentre national study.}, journal = {Ann Rheum Dis}, volume = {76}, year = {2017}, month = {2017 Oct}, pages = {1648-1656}, abstract = {

OBJECTIVES: To analyse the prevalence of mutations in patients diagnosed with early onset livedo reticularis and/or haemorrhagic/ischaemic strokes in the context of inflammation or polyarteritis nodosa (PAN). Forty-eight patients from 43 families were included in the study.

METHODS: Direct sequencing of was performed by Sanger analysis. Adenosine deaminase 2 (ADA2) enzymatic activity was analysed in monocyte isolated from patients and healthy controls incubated with adenosine and with or without an ADA1 inhibitor.

RESULTS: Biallelic homozygous or compound heterozygous mutations were detected in 15/48 patients. A heterozygous disease-associated mutation (p.G47V) was observed in two affected brothers. The mean age of onset of the genetically positive patients was 24 months (6 months to 7 years). Ten patients displayed one or more cerebral strokes during their disease course. Low immunoglobulin levels were detected in six patients. Thalidomide and anti-TNF (tumour necrosis factor) blockers were the most effective drugs. Patients without mutations had a later age at disease onset, a lower prevalence of neurological and skin manifestations; one of these patients displayed all the clinical features of adenosine deaminase 2deficiency (DADA2) and a defective enzymatic activity suggesting the presence of a missed mutation or a synthesis defect.

CONCLUSIONS: DADA2 accounts for paediatric patients diagnosed with PAN-like disease and strokes and might explain an unrecognised condition in patients followed by adult rheumatologist. Timely diagnosis and treatment with anti-TNF agents are crucial for the prevention of severe complications of the disease. Functional assay to measure ADA2 activity should complement genetic testing in patients with non-confirming genotypes.

}, keywords = {Adenosine Deaminase, Adolescent, Age of Onset, Case-Control Studies, Child, Child, Preschool, DNA Mutational Analysis, Female, Heterozygote, Homozygote, Humans, Immunoglobulins, Immunosuppressive Agents, Infant, Intercellular Signaling Peptides and Proteins, Italy, Livedo Reticularis, Male, Pedigree, Polyarteritis Nodosa, Stroke, Thalidomide, Tumor Necrosis Factor-alpha, Young Adult}, issn = {1468-2060}, doi = {10.1136/annrheumdis-2016-210802}, author = {Caorsi, Roberta and Penco, Federica and Grossi, Alice and Insalaco, Antonella and Omenetti, Alessia and Alessio, Maria and Conti, Giovanni and Marchetti, Federico and Picco, Paolo and Tommasini, Alberto and Martino, Silvana and Malattia, Clara and Gallizi, Romina and Podda, Rosa Anna and Salis, Annalisa and Falcini, Fernanda and Schena, Francesca and Garbarino, Francesca and Morreale, Alessia and Pardeo, Manuela and Ventrici, Claudia and Passarelli, Chiara and Zhou, Qing and Severino, Mariasavina and Gandolfo, Carlo and Damonte, Gianluca and Martini, Alberto and Ravelli, Angelo and Aksentijevich, Ivona and Ceccherini, Isabella and Gattorno, Marco} } @article {1694, title = {Abatacept improves health-related quality of life, pain, sleep quality, and daily participation in subjects with juvenile idiopathic arthritis.}, journal = {Arthritis Care Res (Hoboken)}, volume = {62}, year = {2010}, month = {2010 Nov}, pages = {1542-51}, abstract = {

OBJECTIVE: To assess health-related quality of life (HRQOL) in abatacept-treated children/adolescents with juvenile idiopathic arthritis (JIA).

METHODS: In this phase III, double-blind, placebo-controlled trial, subjects with active polyarticular course JIA and an inadequate response/intolerance to >=1 disease-modifying antirheumatic drug (including biologics) received abatacept 10 mg/kg plus methotrexate (MTX) during the 4-month open-label period (period A). Subjects achieving the American College of Rheumatology Pediatric 30 criteria for improvement (defined "responders") were randomized to abatacept or placebo (plus MTX) in the 6-month double-blind withdrawal period (period B). HRQOL assessments included 15 Child Health Questionnaire (CHQ) health concepts plus the physical (PhS) and psychosocial summary scores (PsS), pain (100-mm visual analog scale), the Children{\textquoteright}s Sleep Habits Questionnaire, and a daily activity participation questionnaire.

RESULTS: A total of 190 subjects from period A and 122 from period B were eligible for analysis. In period A, there were substantial improvements across all of the CHQ domains (greatest improvement was in pain/discomfort) and the PhS (8.3 units) and PsS (4.3 units) with abatacept. At the end of period B, abatacept-treated subjects had greater improvements versus placebo in all domains (except behavior) and both summary scores. Similar improvement patterns were seen with pain and sleep. For participation in daily activities, an additional 2.6 school days/month and 2.3 parents{\textquoteright} usual activity days/month were gained in period A responders with abatacept, and further gains were made in period B (1.9 versus 0.9 [P = 0.033] and 0.2 versus -1.3 [P = 0.109] school days/month and parents{\textquoteright} usual activity days/month, respectively, in abatacept- versus placebo-treated subjects).

CONCLUSION: Improvements in HRQOL were observed with abatacept, providing real-life tangible benefits to children with JIA and their parents/caregivers.

}, keywords = {Adolescent, Arthritis, Juvenile, Child, Double-Blind Method, Female, Health Status, Humans, Immunoconjugates, Male, Pain, Quality of Life, Questionnaires, Sleep Stages}, issn = {2151-4658}, doi = {10.1002/acr.20283}, author = {Ruperto, Nicolino and Lovell, Daniel J and Li, Tracy and Sztajnbok, Flavio and Goldenstein-Schainberg, Claudia and Scheinberg, Morton and Penades, Inmaculada Calvo and Fischbach, Michael and Alcala, Javier Orozco and Hashkes, Philip J and Hom, Christine and Jung, Lawrence and Lepore, Loredana and Oliveira, Sheila and Wallace, Carol and Alessio, Maria and Quartier, Pierre and Cortis, Elisabetta and Eberhard, Anne and Simonini, Gabriele and Lemelle, Irene and Chalom, Elizabeth Candell and Sigal, Leonard H and Block, Alan and Covucci, Allison and Nys, Marleen and Martini, Alberto and Giannini, Edward H} }