Pediatr Infect Vaccine.  2018 Dec;25(3):113-122. 10.14776/piv.2018.25.e7.

The First Report on Clinical Manifestation of Cryopyrin-Associated Periodic Syndrome in Korean Children

• Kim KY
• Kim SY
• Park SE
• Lee J
• Lee H
• Lee S
• Kim JG

• KMID: 2428248
• DOI: http://doi.org/10.14776/piv.2018.25.e7

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.

Keyword

Cryopyrin-associated periodic syndrome; Familial Cold Autoinflammatory Syndrome; Muckle-Wells Syndrome, Republic of Korea

MeSH Terms

Arthralgia
Atrophy
Blood Sedimentation
Bone Diseases, Metabolic
Brain
C-Reactive Protein
Cartilage
Child*
Chorioretinitis
Conjunctivitis
Cryopyrin-Associated Periodic Syndromes*
Diagnosis
Edema
Epiphyses
Exanthema
Exons
Femur
Fever
Hearing Loss
Humans
Intellectual Disability
Interleukin 1 Receptor Antagonist Protein
Joints
Korea
Magnetic Resonance Imaging
Myalgia
Parturition
Patella
Uveitis
C-Reactive Protein
Interleukin 1 Receptor Antagonist Protein

Figure

• 

  Fig. 1 Knee swelling in a 10-year-old boy diagnosed with CAPS. Abbreviations: CAPS, cryopyrin-associated periodic syndrome.

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  Fig. 2 Patellar ossification in a 10-year-old boy diagnosed with CAPS. Abbreviations: CAPS, cryopyrin-associated periodic syndrome.

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  Fig. 3 Brain MRI of a 9-year-old boy showed brain atrophy and enlarged ventricles. Abbreviations: MRI, magnetic resonance imaging.

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  Fig. 4 All the patients had mutations in exon 3 of CIAS1/NLRP3 on chromosome 1q44. Eight different sequence variants were detected, and all were missense mutations. Six have already been reported in other countries (p.Glu304Lys, p.Asp303Gly, p.Met664Thr, p.Tyr572Cys, p.Arg262Trp, and p.Asp303His). Abbreviations: CIAS1, cold-induced autoinflammatory syndrome 1; NLRP3, nucleotide-binding domain, leucine-rich family, pyrin domain-containg-3; UTR, untranslated region.

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