Objective. Periodic fever syndrome (PFS) conditions are characterized by recurrent attacks of fever and localized inflammation. This study examined the diagnostic pathway and treatments at tertiary centers for familial Mediterranean fever (FMF), tumor necrosis factor receptor-associated periodic syndrome (TRAPS), and mevalonate kinase deficiency (MKD)/hyperimmunoglobulinemia D syndrome (HIDS). Methods. PFS specialists at medical centers in the US, the European Union, and the eastern Mediterranean participated in a retrospective chart review, providing de-identified data in an electronic case report form. Patients were treated between 2008 and 2012, with at least 1 year of followup; all had clinical and/or genetically proven disease and were on/eligible for biologic treatment. Results. A total of 134 patients were analyzed: FMF (n549), TRAPS (n547), and MKD/HIDS (n538). Fever was commonly reported as severe across all indications. Other frequently reported severe symptoms were serositis for FMF patients and elevated acute-phase reactants and gastrointestinal upset for TRAPS and MKD/HIDS. A long delay from disease onset to diagnosis was seen within TRAPS and MKD/HIDS (5.8 and 7.1 years, respectively) compared to a 1.8-year delay in FMF patients. An equal proportion of TRAPS patients first received anti-interleukin-1 (anti-IL-1) and anti-tumor necrosis factor (anti-TNF) biologic agents, whereas IL-1 blockade was the main choice for FMF patients resistant to colchicine and MKD/HIDS patients. For TRAPS patients, treatment with anakinra versus anti-TNF treatments as first biologic agent resulted in significantly higher clinical and biochemical responses (P=0.03 and P< 0.01, respectively). No significant differences in responses were observed between biologic agents among other cohorts. Conclusion. Referral patterns and diagnostic delays highlight the need for greater awareness and improved diagnostics for PFS. This real-world treatment assessment supports the need for further refinement of treatment practices.
WOS: 000374731400001 ; PubMed ID: 27055417 ; Background: In this study, we examined the efficacy and safety of a once-daily dosage schema of colchicine compared with a twice-daily dosage schema in pediatric patients with familial Mediterranean fever (FMF). Methods: In this 24-week, multicenter, randomized controlled noninferiority trial, pediatric patients newly diagnosed with FMF carrying a homozygous or compound heterozygous mutation and not receiving any treatment were included. Patients were randomly assigned using a block randomization method to receive treatment with a once-or twice-daily dosage. Clinical and laboratory characteristics and medication side effects were recorded and compared between groups. The study was carried out in compliance with Good Clinical Practice and the Consolidated Standards for Reporting of Trials (CONSORT) statement. Results: A total of 92 patients were selected, and 79 patients completed the study. There were 42 patients in the once-daily dosage group and 37 in the twice-daily dosage group. The results indicated that the once-daily dosage was not inferior to the twice-daily dosage regarding decrease in attack frequency and duration as well as improvement in clinical findings and Mor severity scores. Alterations in laboratory findings indicating inflammation, such as erythrocyte sedimentation rate, C-reactive protein, and serum amyloid A, were similar in both groups. The rates of drug side effects were similar between the once-and twice-daily dosage groups, implying comparable safety of colchicine, with the exception of diarrhea, which was slightly higher in the once-daily dosage group. Conclusions: Using colchicine with either a once-or twice-daily dosage provides similar clinical and laboratory improvements. Considering both efficacy and safety, colchicine can be prescribed with a once-daily dosage. ; Scientific Council of the Gulhane Military Medical Academy School of Medicine ; This study was funded by the Scientific Council of the Gulhane Military Medical Academy School of Medicine and is registered with ClinicalTrials.gov with the number NCT 1491-1437-11/1539 and the identifier NCT02602028.
Objectives Juvenile idiopathic arthritis (JIA) is a heterogeneous group of conditions unified by the presence of chronic childhood arthritis without an identifiable cause. Systemic JIA (sJIA) is a rare form of JIA characterised by systemic inflammation. sJIA is distinguished from other forms of JIA by unique clinical features and treatment responses that are similar to autoinflammatory diseases. However, approximately half of children with sJIA develop destructive, long-standing arthritis that appears similar to other forms of JIA. Using genomic approaches, we sought to gain novel insights into the pathophysiology of sJIA and its relationship with other forms of JIA. Methods We performed a genome-wide association study of 770 children with sJIA collected in nine countries by the International Childhood Arthritis Genetics Consortium. Single nucleotide polymorphisms were tested for association with sJIA. Weighted genetic risk scores were used to compare the genetic architecture of sJIA with other JIA subtypes. Results The major histocompatibility complex locus and a locus on chromosome 1 each showed association with sJIA exceeding the threshold for genome-wide significance, while 23 other novel loci were suggestive of association with sJIA. Using a combination of genetic and statistical approaches, we found no evidence of shared genetic architecture between sJIA and other common JIA subtypes. Conclusions The lack of shared genetic risk factors between sJIA and other JIA subtypes supports the hypothesis that sJIA is a unique disease process and argues for a different classification framework. Research to improve sJIA therapy should target its unique genetics and specific pathophysiological pathways. ; Intramural Research Programs of the National Institute of Arthritis and Musculoskeletal and Skin Diseases ; National Human Genome Research Institute of the National Institutes of Health (NIH) ; NIH ; Arthritis Research UK ; German Federal Ministry of Education and Research (BMBF) ; Val A. Browning Charitable Foundation ; Marcus Foundation ; Proyecto de Excelencia of the Andalousian Government (MA-R) ; Swedish Association Against Rheumatism (MA-R) ; Wellcome Trust ; National Institute for Health Research Biomedical Research Unit Funding Scheme ; Manchester Academic Health Sciences Centre (MAHSC) ; SPARKS UK ; Medical Research Council ; UK National Institute for Health Research GOSH Biomedical Research Centre ; Canadian Institutes of Health Research ; Arthritis Society (CIHR) ; Canadian Arthritis Network ; Cincinnati Children's Research Foundation and its Cincinnati Genomic Control Cohort ; USA NIH research programme ; UK Medical Research Council ; Natl Inst Arthrit & Musculoskeletal & Skin Dis, Natl Inst Hlth, US Dept Hlth & Human Serv, Translat Genet & Genom Unit, Bethesda, MD USA ; NHGRI, Natl Inst Hlth, Inflammatory Dis Sect, US Dept Hlth & Human Serv, Bethesda, MD 20892 USA ; Manchester Acad Hlth Sci Ctr, Arthrit Res UK Ctr Genet & Genom, Ctr Musculoskeletal Res, Manchester, Lancs, England ; Wellcome Trust Sanger Inst, Human Genet, Hinxton, England ; Univ Cincinnati, Coll Med, Dept Pediat, Cincinnati, OH USA ; Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH 45229 USA ; Univ Hosp Munster, Dept Pediat Rheumatol & Immunol, Munster, Germany ; Univ Genoa, Dept Pediat, Genoa, Italy ; Giannina Gaslini Inst, Pediat Unit 2, Genoa, Italy ; Hacettepe Univ, Dept Pediat Rheumatol, Ankara, Turkey ; Emory Univ, Sch Med, Dept Pediat & Human Genet, Atlanta, GA 30322 USA ; Childrens Healthcare Atlanta, Atlanta, GA USA ; Cleveland Clin, Dept Pediat, Cleveland, OH 44106 USA ; Univ Utah, Dept Pediat, Salt Lake City, UT USA ; Albert Einstein Coll Med, Dept Pediat, Bronx, NY 10467 USA ; Childrens Hosp Montefiore, Bronx, NY USA ; Stanford Univ, Dept Pediat, Stanford, CA 94305 USA ; Hosp Pediat Garrahan, Serv Immunol & Rheumatol, Buenos Aires, DF, Argentina ; Univ Fed Sao Paulo, Dept Pediat, Sao Paulo, Brazil ; Univ Fed Rio de Janeiro, Rio De Janeiro, Brazil ; Univ Toronto, Dept Pediat, Toronto, ON, Canada ; Univ Toronto, Dept Pediat, Toronto, ON, Canada ; Univ Toronto, Inst Med Sci, Toronto, ON, Canada ; Univ Saskatchewan, Dept Pediat, Saskatoon, SK, Canada ; UCL, Inst Child Hlth, London, England ; UCL, Ctr Paediat & Adolescent Rheumatol, London, England ; Univ Barcelona, Hosp Sant Joan Deu, Pediat Rheumatol Unit, Barcelona, Spain ; German Ctr Pediat & Adolescent Rheumatol, Garmisch Partenkirchen, Germany ; Univ Hosp Cal Gustav Carus, Dresden, Germany ; Charite, Dept Rheumatol & Clin Immunol, Berlin, Germany ; German Rheumatism Res Ctr, Epidemiol Unit, Berlin, Germany ; Rhein Westfal TH Aachen, Dept Pediat, Aachen, Germany ; Univ Manchester, Manchester Acad Hlth Sci Ctr, Cent Manchester Univ Hosp NHS Fdn Trust, Natl Inst Hlth Res Manchester Musculoskeletal Bio, Manchester, Lancs, England ; Univ Pittsburgh, Dept Med, Pittsburgh, PA USA ; Univ Pittsburgh, Dept Human Genet, Pittsburgh, PA USA ; Cleveland Clin, Dept Gastroenterol & Hepatol, Cleveland, OH 44106 USA ; Cleveland Clin, Dept Pathobiol, Cleveland, OH 44106 USA ; Icahn Sch Med Mt Sinai, Dept Genet & Genom Sci, New York, NY 10029 USA ; Hosp Sick Children, Ctr Appl Gen, Toronto, ON, Canada ; Pfizer Univ Granada Andalusian Govt, Ctr Genom & Oncol Res, Granada, Spain ; Karolinska Inst, Inst Environm Med, Unit Chron Inflammatory Dis, Solna, Sweden ; Interdisciplinary Cluster Appl Genoprote Univ Lie, Liege, Belgium ; Barcelona Inst Sci & Technol, Ctr Gene Regulat, Barcelona, Spain ; Univ Pompeu Fabra UPF, Barcelona, Spain ; Sidra Med & Res Ctr, Doha, Qatar ; Istanbul Univ, Istanbul Fac Med, Istanbul, Turkey ; Wake Forest Univ Hlth Sci, Dept Biostat Sci, Winston Salem, NC USA ; Univ Fed Sao Paulo, Dept Pediat, Sao Paulo, Brazil ; Intramural Research Programs of the National Institute of Arthritis and Musculoskeletal and Skin Diseases: Z01-AR041198 ; National Human Genome Research Institute of the National Institutes of Health (NIH): Z01-HG200370 ; NIH: R01-AR059049 ; NIH: R01AR061297 ; NIH: R01-AR060893 ; NIH: P30-AR47363 ; NIH: P01-AR48929 ; NIH: AG030653 ; NIH: AG041718 ; NIH: AG005133 ; NIH: U01-DK062420 ; NIH: R01-DK076025 ; Arthritis Research UK: 20385 ; Arthritis Research UK: 20542 ; German Federal Ministry of Education and Research (BMBF): 01ER0813 ; Proyecto de Excelencia of the Andalousian Government (MA-R): CTS-2548 ; Wellcome Trust: 098051 ; Wellcome Trust: 076113/C/04/Z ; Wellcome Trust: 068545/Z/02 ; SPARKS UK: 08ICH09 ; SPARKS UK: 12ICH08 ; Medical Research Council: MR/M004600/1 ; Arthritis Society (CIHR): 82517 ; Canadian Arthritis Network: SRI-IJD-01 ; USA NIH research programme: RP-PG-0310-1002 ; UK Medical Research Council: G0000934 ; Web of Science
