Pediatric Infection and Vaccine

The Korean Society of Pediatric Infectious Diseases (대한소아감염학회)
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The First Report on Clinical Manifestation of Cryopyrin-Associated Periodic Syndrome in Korean Children

  • Kim, Kwang Yeon (Department of Pediatrics, Seoul National University College of Medicine) ;
  • Kim, Sae Yun (Department of Pediatrics, Kangwon National University Hospital) ;
  • Park, Su Eun (Department of Pediatrics, Pusan National University Yangsan Hospital) ;
  • Lee, Jina (Department of Pediatrics, Asan Medical Center, University of Ulsan College of Medicine) ;
  • Lee, Hyunju (Department of Pediatrics, Seoul National University Bundang Hospital) ;
  • Lee, Soyoung (Department of Pediatrics, Seoul National University College of Medicine) ;
  • Kim, Joong Gon (Department of Pediatrics, Seoul National University College of Medicine)
  • Received : 2017.09.01
  • Accepted : 2018.09.17
  • Published : 2018.12.25
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Abstract

Purpose: The aim of this study was to evaluate the clinical characteristics of children diagnosed as cryopyrin-associated periodic syndrome (CAPS) in Korea. Methods: Diagnosis was made based on clinical features and confirmed by a mutation in the cold-induced autoinflammatory syndrome 1 (CIAS1) gene. Especially, osteocartilaginous overgrowth in the patella or distal femur was so characteristic that its presence warranted a diagnosis of chronic infantile neurologic cutaneous and articular/NOMID. Results: We observed the clinical features of 9 Korean CAPS patients. All the patients suffered from an urticarial rash with recurrent fever. Among the 9 patients, 6 presented with rash and 4 with fever on the 1st or 2nd days of birth. Eight patients showed myalgia, and 7 patients showed arthralgia in the joints, and 6 patients showed radiologic findings of arthropathy including cupping of the metaphysis, excessive growth of the epiphysis, osteopenia or overgrowth of the cartilage. Four patients showed brain atrophy, enlarged ventricles or leptomeningeal enhancement on magnetic resonance imaging. Intellectual disability was observed in 1 patient. Five patients had eye involvement as conjunctivitis, uveitis, chorioretinitis, avascular area or papillary edema, and 3 patients showed progressive hearing loss. All 9 patients showed increased C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR). Conclusions: All the patients carried a mutation on exon 3 of the CIAS1 gene. After the anakinra (interleukin-1 receptor antagonist) therapy, the fever and rash immediately disappeared, and CRP and ESR were improved.

목적: 국내에서 cryopyrin-associated periodic syndrome (CAPS) 환자로 진단된 소아들의 임상 양상을 확인하고자 하였다. 방법: 2000년부터 2015년까지 서울대학교 어린이병원에서 CAPS로 진단받은 9명 소아들의 의무기록을 분석하였다. CAPS의 진단은 처음에는 임상 양상과 병력에 근거하였고 CIAS1 유전자의 돌연변이를 통해 최종 확진하였다. 결과:모든환자는재발하는열및두드러기발진이있었다. 9명의환자중 6명은발진이그리고 4명은발열이출생 1일또는 2일 안에 있었다. 근육통을 보인 환자는 8명이었고, 관절통이 있는 환자는 7명이었다. 이들은 방사선학적 소견 상 골단의 과도한 성장, 골감소증 또는 연골의 과성장과 같은 소견을 보였다. 4명의 환자는 뇌위축, 뇌실 확장 또는 자기공명영상에서 연수막 증대 소견을 보였다. 지적 장애가 1명에서 관찰되었다. 5명의 환자가 결막염, 포도막염, 맥락 망막염, 유두 부종으로 시력에 영향을 받았으며 3명은 진행성 난청을 보였다. 9명 모두에서 초기 C-반응성 단백질과 적혈구 침강속도가 증가되었다. 모든 환자는 CIAS1 유전자의 exon 3에서 돌연변이를 보였다. Anakinra 치료 후 발열과 발진이 사라졌으며 C-반응성 단백질과 적혈구 침강 속도가 호전되었다. 결론: 이 연구는 국내에서 처음으로 CAPS 환자들의 임상 증상을 고찰한 논문으로 향후 새로이 환자들을 진단하는데 유용할 것이다. 또한 환자들의 장기적인 합병증을 예방하기 위해 이른 나이부터 발생하는 반복적인 발열과 발진이 있는 소아에서 조기에 CAPS를 진단하고 치료하는 것이 중요하다.

Keywords

References

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