Treatment preferences in juvenile idiopathic arthritis – a comparative analysis in two health care systems

<p>Abstract</p> <p>Background</p> <p>Variations in the treatment of juvenile idiopathic arthritis (JIA) may impact on quality of care. The objective of this study was to identify and compare treatment approaches for JIA in two health care systems.</p> <p>Methods</p> <p>Paediatric rheumatologists in Canada (n=58) and Germany/Austria (n=172) were surveyed by email, using case-based vignettes for oligoarticular and seronegative polyarticular JIA. Data were analysed using descriptive statistics; responses were compared using univariate analysis.</p> <p>Results</p> <p>Total response rate was 63%. Physicians were comparable by age, level of training and duration of practice, with more Canadians based in academic centres. For initial treatment of oligoarthritis, only approximately half of physicians in both groups used intra-articular steroids. German physicians were more likely to institute DMARD treatment in oligoarthritis refractory to NSAID (p<0.001). Canadian physicians were more likely to switch to a different DMARD rather than a biologic agent in polyarthritis refractory to initial DMARD therapy. For oligoarthritis and polyarthritis, respectively, 86% and 90% of German physicians preferred regular physiotherapy over home exercise, compared to 14% and 15% in Canada. Except for a Canadian preference for naproxen in oligoarthritis, no significant differences were found for NSAID, intra-articular steroid preparations, initial DMARD and initial biologic treatment.</p> <p>Conclusions</p> <p>Treatment of oligo- and polyarticular JIA with DMARD is mostly uniform, with availability and funding obviously influencing physician choice. Usage of intra-articular steroids is variable within physician groups. Physiotherapy has a fundamentally different role in the two health care systems.</p

Diagnostic criteria for cryopyrin-associated periodic syndrome (CAPS)

Cryopyrin-associated periodic syndrome (CAPS) is a rare, heterogeneous disease entity associated with NLRP3 gene mutations and increased interleukin-1 (IL-1) secretion. Early diagnosis and rapid initiation of IL-1 inhibition prevent organ damage. The aim of the study was to develop and validate diagnostic criteria for CAPS. An innovative process was followed including interdisciplinary team building, item generation: review of CAPS registries, systematic literature review, expert surveys, consensus conferences for item refinement, item reduction and weighting using 1000Minds decision software. Resulting CAPS criteria were tested in large cohorts of CAPS cases and controls using correspondence analysis. Diagnostic models were explored using sensitivity analyses. The international team included 16 experts. Systematic literature and registry review identified 33 CAPS-typical items; the consensus conferences reduced these to 14. 1000Minds exercises ranked variables based on importance for the diagnosis. Correspondence analysis determined variables consistently associated with the diagnosis of CAPS using 284 cases and 837 controls. Seven variables were significantly associated with CAPS (p<0.001). The best diagnosis model included: Raised inflammatory markers (C-reactive protein/serum amyloid A) plus ≥two of six CAPS-typical symptoms: urticaria-like rash, cold-triggered episodes, sensorineural hearing loss, musculoskeletal symptoms, chronic aseptic meningitis and skeletal abnormalities. Sensitivity was 81%, specificity 94%. It performed well for all CAPS subtypes and regardless of NLRP3 mutation. The novel approach integrated traditional methods of evidence synthesis with expert consensus, web-based decision tools and innovative statistical methods and may serve as model for other rare diseases. These criteria will enable a rapid diagnosis for children and adults with CAPS

Diagnostic criteria for cryopyrin-associated periodic syndrome (CAPS)

Cryopyrin-associated periodic syndrome (CAPS) is a rare, heterogeneous disease entity associated with NLRP3 gene mutations and increased interleukin-1 (IL-1) secretion. Early diagnosis and rapid initiation of IL-1 inhibition prevent organ damage. The aim of the study was to develop and validate diagnostic criteria for CAPS. An innovative process was followed including interdisciplinary team building, item generation: review of CAPS registries, systematic literature review, expert surveys, consensus conferences for item refinement, item reduction and weighting using 1000Minds decision software. Resulting CAPS criteria were tested in large cohorts of CAPS cases and controls using correspondence analysis. Diagnostic models were explored using sensitivity analyses. The international team included 16 experts. Systematic literature and registry review identified 33 CAPS-typical items; the consensus conferences reduced these to 14. 1000Minds exercises ranked variables based on importance for the diagnosis. Correspondence analysis determined variables consistently associated with the diagnosis of CAPS using 284 cases and 837 controls. Seven variables were significantly associated with CAPS (p= two of six CAPS-typical symptoms: urticaria-like rash, cold-triggered episodes, sensorineural hearing loss, musculoskeletal symptoms, chronic aseptic meningitis and skeletal abnormalities. Sensitivity was 81%, specificity 94%. It performed well for all CAPS subtypes and regardless of NLRP3 mutation. The novel approach integrated traditional methods of evidence synthesis with expert consensus, web-based decision tools and innovative statistical methods and may serve as model for other rare diseases. These criteria will enable a rapid diagnosis for children and adults with CAPS

Diagnostic criteria for cryopyrin-associated periodic syndrome (CAPS)

Cryopyrin-associated periodic syndrome (CAPS) is a rare, heterogeneous disease entity associated with NLRP3 gene mutations and increased interleukin-1 (IL-1) secretion. Early diagnosis and rapid initiation of IL-1 inhibition prevent organ damage. The aim of the study was to develop and validate diagnostic criteria for CAPS. An innovative process was followed including interdisciplinary team building, item generation: review of CAPS registries, systematic literature review, expert surveys, consensus conferences for item refinement, item reduction and weighting using 1000Minds decision software. Resulting CAPS criteria were tested in large cohorts of CAPS cases and controls using correspondence analysis. Diagnostic models were explored using sensitivity analyses. The international team included 16 experts. Systematic literature and registry review identified 33 CAPS-typical items; the consensus conferences reduced these to 14. 1000Minds exercises ranked variables based on importance for the diagnosis. Correspondence analysis determined variables consistently associated with the diagnosis of CAPS using 284 cases and 837 controls. Seven variables were significantly associated with CAPS (p<0.001). The best diagnosis model included: Raised inflammatory markers (C-reactive protein/serum amyloid A) plus ≥two of six CAPS-typical symptoms: urticaria-like rash, cold-triggered episodes, sensorineural hearing loss, musculoskeletal symptoms, chronic aseptic meningitis and skeletal abnormalities. Sensitivity was 81%, specificity 94%. It performed well for all CAPS subtypes and regardless of NLRP3 mutation. The novel approach integrated traditional methods of evidence synthesis with expert consensus, web-based decision tools and innovative statistical methods and may serve as model for other rare diseases. These criteria will enable a rapid diagnosis for children and adults with CAPS

Acid Ceramidase Deficiency is characterized by a unique plasma cytokine and ceramide profile that is altered by therapy

Acid Ceramidase Deficiency (Farber disease, FD) is an ultra-rare Lysosomal Storage Disorder that is poorly understood and often misdiagnosed as Juvenile Idiopathic Arthritis (JIA). Hallmarks of FD are accumulation of ceramides, widespread macrophage infiltration, splenomegaly, and lymphocytosis. The cytokines involved in this abnormal hematopoietic state are unknown. There are dozens of ceramide species and derivatives, but the specific ones that accumulate in FD have not been investigated. We used a multiplex assay to analyze cytokines and mass spectrometry to analyze ceramides in plasma from patients and mice with FD, controls, Farber patients treated by hematopoietic stem cell transplantation (HSCT), JIA patients, and patients with Gaucher disease. KC, MIP-1 alpha, and MCP-1 were sequentially upregulated in plasma from FD mice. MCP-1, IL-10, IL-6, IL-12, and VEGF levels were elevated in plasma from Farber patients but not in control or JIA patients. C16-Ceramide (C16-Cer) and dhC16-Cer were upregulated in plasma from FD mice. a-OH-C18-Cer, dhC12-Cer, dhC24:1-Cer, and C22:1-Cer-1P accumulated in plasma from patients with FD. Most cytokines and only a-OH-C18-Cer returned to baseline levels in HSCT-treated Farber patients. Sphingosines were not altered. Chitotriosidase activity was also relatively low. A unique cytokine and ceramide profile was seen in the plasma of Farber patients that was not observed in plasma from HSCT-treated Farber patients, JIA patients, or Gaucher patients. The cytokine profile can potentially be used to prevent misdiagnosis of Farber as JIA and to monitor the response to treatment. Further understanding of why these signaling molecules and lipids are elevated can lead to better understanding of the etiology and pathophysiology of FD and inform development of future treatments. (C) 2016 Elsevier B.V. All rights reserved.Rare Disease FoundationBC Children's Hospital FoundationNational Institutes of HealthVaincre les Maladies LysosomalesPlexcera TherapeuticsUniv Toronto, Inst Med Sci, Toronto, ON M5G 1L7, CanadaUniv Toronto, Dept Med Biophys, Toronto, ON M5G 1L7, CanadaMed Univ South Carolina, Dept Microbiol & Immunol, Hollings Canc Ctr, Charleston, SC 29425 USAUniv Calgary, Alberta Childrens Hosp, Med Genet & Pediat, Calgary, AB T3B 6A8, CanadaCtr Hosp Univ Sherbrooke, Dept Genet, Sherbrooke, PQ J1G 2E8, CanadaMcGill Univ, Dept Med Genet, Montreal, PQ H3A 0G4, CanadaMcGill Univ, Dept Pediat, Montreal, PQ H3A 0G4, CanadaUniv Milano Bicocca, San Gerardo Hosp, Dept Pediat, I-20126 Monza, ItalyG Gaslini Childrens Hosp, I-16148 Genoa, ItalyGerman Ctr Paediat & Adolescent Rheumatol, D-82467 Garmisch Partenkirchen, GermanyKagoshima Univ, Grad Sch Med & Dent Sci, Div Hematol & Immunol, Ctr Chron Viral Dis, Kagoshima 8908544, JapanKarolinska Univ Hosp, Pediat Rheumatol, S-17176 Stockholm, SwedenDokuz Eylul Univ, Pediat Rheumatol, TR-35210 Izmir, TurkeyDokuz Eylul Univ, Gastroenterol & Metab Dis, TR-35210 Izmir, TurkeyUniv Cordoba, Metab Dis, RA-14002 Cordoba, ArgentinaMed Univ Greifswald, Dept Paediat Oncol & Haematol, D-17475 Greifswald, GermanyGoethe Univ, Dept Paediat Oncol & Haematol, D-60323 Frankfurt, GermanyUniv Glasgow, Pediat Rheumatol, Glasgow G12 8QQ, Lanark, ScotlandNotre Dame De Secours Univ Hosp, Pediat Rheumatol, Byblos, LebanonUniv Fed Sao Paulo, Pediat Rheumatol, BR-04023900 Sao Paulo, BrazilUniv Sao Paulo, Hosp Ribeirao Preto, Neurogenet, BR-04023900 Sao Paulo, BrazilBernard & Millie Duker Childrens Hosp, Albany Med Ctr, Pediat Rheumatol, Albany, NY 12208 USAChildrens Natl Hlth Syst, Metab Dis, Washington, DC 20010 USAPlexcera Therapeut, New York, NY 10029 USAIcahn Sch Med Mt Sinai, Dept Genet & Genom Sci, New York, NY 10029 USACHU Purpan, Inst Federatif Biol, Lab Biochim Metab, F-31037 Toulouse 1, FranceUniv Hlth Network, Toronto, ON M5G 1L7, CanadaMed Coll Wisconsin, 8701 Watertown Plank Rd,CRI C4540, Milwaukee, WI 53226 USAUniv Fed Sao Paulo, Pediat Rheumatol, BR-04023900 Sao Paulo, BrazilNIH: 1R21NS078191-01A1NIH: R01 DK54830Web of Scienc

Molecular and clinical spectrum of type I plasminogen deficiency: a series of 50 patients

Severe type I plasminogen (PLG) deficiency has been causally linked to a rare chronic inflammatory disease of the mucous membranes that may be life threatening. Here we report clinical manifestations, PLG plasma levels, and molecular genetic status of the PLG gene of 50 patients. The most common clinical manifestations among these patients were ligneous conjunctivitis (80%) and ligneous gingivitis (34%), followed by less common manifestations such as ligneous vaginitis (8%), and involvement of the respiratory tract (116%), the ears (14%), or the gastrointestinal tract (2%). Four patients showed congenital occlusive hydrocephalus, 2 with Dandy-Walker malformation of cerebellum. Venous thrombosis was not observed. In all patients, plasma PLG levels were markedly reduced. In 38 patients, distinct mutations in the PLG gene were identified. The most common genetic alteration was a K19E mutation found in 34% of patients. Transient in vitro expression of PLG mutants R134K, delK212, R216H, P285T P285A, T319_N320insN, and R776H in transfected COS-7 cells revealed significantly impaired secretion and increased degradation of PLG. These results demonstrate impaired secretion of mutant PLG proteins as a common molecular pathomechanism in type I PLG deficiency.Wo