title: Clinical and Genetic Features of Korean Patients with Recurrent Fever and Multi-System Inflammation without Infectious or Autoimmune Evidence.
abstract: Autoinflammatory disease (AID) is a newly proposed category of disorders characterized by unprovoked episodes of inflammation without any infectious or autoimmune evidence. We aimed to characterize the clinical and genetic features of patients who had recurrent fever and multi-system inflammation but remain unclassified for any established AIDs. Medical records of 1,777 patients who visited our Rheumatology Clinic between March 2009 and December 2010 were reviewed to identify those who met the following criteria; 1) presence of fever, 2) inflammation in two or more organ systems, 3) recurrent nature of fever or inflammation, 4) no evidence of infection or malignancy, 5) absence of high titer autoantibodies, and 6) failure to satisfy any classification criteria for known AIDs. Genotyping was performed for common missense variants in MEFV, NOD2/CARD15, and TNFRSF1A. A small number of patients (17/1,777, 0.95%) were identified to meet the above criteria. Muco-cutaneous and musculoskeletal features were most common, but there was a considerable heterogeneity in symptom combination. Although they did not satisfy any established classification criteria for AIDs, substantial overlap was observed between the clinical spectrum of these patients and known AIDs. According to the newly proposed Eurofever criteria for periodic fevers, eleven of them were classified as TNF receptor-associated periodic syndrome and two as mevalonate kinase deficiency. However, no examined genetic variants including those in TNFRSF1A were found in these patients. A new set of classification criteria needs to be developed and validated for Asian patients with unclassified AIDs.
authors.affiliation: Division of Rheumatology, Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea.
authors.forename: Ji Ae
authors.identifier: 0000-0003-1620-0376
authors.initials: JA
authors.lastname: Yang
authors.affiliation: Division of Rheumatology, Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea.
authors.forename: Ji Yong
authors.identifier: 0000-0003-3155-3196
authors.initials: JY
authors.lastname: Choi
authors.affiliation: Division of Rheumatology, Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea.
authors.forename: Eun Ha
authors.identifier: 0000-0001-9697-1159
authors.initials: EH
authors.lastname: Kang
authors.affiliation: Division of Rheumatology, Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea.
authors.forename: You-Jung
authors.identifier: 0000-0001-6107-9523
authors.initials: YJ
authors.lastname: Ha
authors.affiliation: Division of Rheumatology, Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea.
authors.forename: Yun Jong
authors.identifier: 0000-0001-7615-8611
authors.initials: YJ
authors.lastname: Lee
authors.affiliation: Division of Rheumatology, Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea.
authors.forename: Yeong Wook
authors.identifier: 0000-0003-3155-3196
authors.initials: YW
authors.lastname: Song
mesh_terms: D000293:Adolescent; D000328:Adult; D003598:Cytoskeletal Proteins / Q000235:genetics; D005260:Female; D005334:Fever / Q000209:etiology*; D005838:Genotype; D056660:Hereditary Autoinflammatory Diseases / Q000145:classification / Q000175:diagnosis* / Q000235:genetics; D006801:Humans; D007249:Inflammation / Q000209:etiology*; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D053473:Nod2 Signaling Adaptor Protein / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D000071198:Pyrin; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000235:genetics; D012008:Recurrence; D056910:Republic of Korea; D012189:Retrospective Studies; D055815:Young Adult
chemical_list: D003598:Cytoskeletal Proteins; C000604192:MEFV protein, human; C429018:NOD2 protein, human; D053473:Nod2 Signaling Adaptor Protein; D000071198:Pyrin; D047888:Receptors, Tumor Necrosis Factor, Type I; C506235:TNFRSF1A protein, human
keywords: Autoinflammatory Disease; Classification; Fever
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