J Korean Med Sci.  2016 Feb;31(2):196-201. 10.3346/jkms.2016.31.2.196.

Clinical and Genetic Features of Korean Patients with Recurrent Fever and Multi-System Inflammation without Infectious or Autoimmune Evidence

• Yang JA
• Choi JY
• Kang EH
• Ha YJ
• Lee YJ
• Song YW

• KMID: 2360042
• DOI: http://doi.org/10.3346/jkms.2016.31.2.196

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.

Keyword

Autoinflammatory Disease; Fever; Classification

MeSH Terms

Adolescent
Adult
Cytoskeletal Proteins/genetics
Female
Fever/*etiology
Genotype
Hereditary Autoinflammatory Diseases/classification/*diagnosis/genetics
Humans
Inflammation/*etiology
Male
Middle Aged
Mutation, Missense
Nod2 Signaling Adaptor Protein/genetics
Polymorphism, Single Nucleotide
Receptors, Tumor Necrosis Factor, Type I/genetics
Recurrence
Republic of Korea
Retrospective Studies
Young Adult
Cytoskeletal Proteins
Nod2 Signaling Adaptor Protein
Receptors, Tumor Necrosis Factor, Type I

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