Early canakinumab therapy for the sensorineural deafness in a family with Muckle-Wells syndrome due to a novel mutation of NLRP3 gene

Yasunori Iida, Hiroyuki Wakiguchi, Fumiko Okazaki, Tamaki Nakamura, Hiroki Yasudo, Makoto Kubo, Kazuma Sugahara, Hiroshi Yamashita, Yutaka Suehiro, Naoko Okayama, Kunio Hashimoto, Naoki Iwamoto, Atsushi Kawakami, Yoshiharu Aoki, Hidetoshi Takada, Shoichi Ohga, Shunji Hasegawa

Research output: Contribution to journalArticle

Abstract

Cryopyrin-associated periodic syndrome (CAPS) is one of the autoinflammatory disorders caused by mutations in NLRP3 gene. The over-production of interleukin (IL)-1β induced by NLRP3 gene mutations plays an important role in the pathophysiology of CAPS. We diagnosed 3 patients with CAPS, who were lineal family members having a novel mutation of NLRP3 gene. The objective of this report is to compare the characteristics of symptoms and differences in the therapeutic responses of them, who had the same mutation. In addition, we aimed to examine the usefulness of cytokine measurement for diagnosis or determination of treatment effect of CAPS. A 5-year-old Japanese boy (proband) came to our hospital because of short stature, reached the diagnosis of Muckle-Wells syndrome (MWS) due to a mutation in NLRP3 gene, which had not been reported so far (p.G328E, c.G983A). His mother and grandmother harbored the same mutation of NLRP3. We measured serum concentrations of cytokines in the proband assessed by flow-cytometric bead array. All of them had episodic skin eruptions with conjunctivitis, hearing loss, and arthralgia, but not periodic fever, cold-triggered episodes, and chronic aseptic meningitis. Only the proband had short stature. Canakinumab therapy led to a prompt relief of symptoms and normalized laboratory data in all patients. Audiograms demonstrated an improved hearing level in the proband, but not two others despite of the same mutation. All cytokines did not show any characteristic findings. Sensorineural hearing loss and itchless rash but not serum cytokine profile deserved attention to the diagnosis and treatment start of CAPS. The early intervention of IL-1β blockade may reduce the chance of complete deafness in patients with CAPS.

Original languageEnglish
Pages (from-to)943-948
Number of pages6
JournalClinical Rheumatology
Volume38
Issue number3
DOIs
Publication statusPublished - Mar 14 2019

Fingerprint

Cryopyrin-Associated Periodic Syndromes
Deafness
Secondary Prevention
Mutation
Genes
Cytokines
Interleukin-1
Aseptic Meningitis
Conjunctivitis
Sensorineural Hearing Loss
Arthralgia
Therapeutics
canakinumab
Exanthema
Serum
Hearing Loss
Hearing
Fever
Mothers
Skin

All Science Journal Classification (ASJC) codes

  • Rheumatology

Cite this

Early canakinumab therapy for the sensorineural deafness in a family with Muckle-Wells syndrome due to a novel mutation of NLRP3 gene. / Iida, Yasunori; Wakiguchi, Hiroyuki; Okazaki, Fumiko; Nakamura, Tamaki; Yasudo, Hiroki; Kubo, Makoto; Sugahara, Kazuma; Yamashita, Hiroshi; Suehiro, Yutaka; Okayama, Naoko; Hashimoto, Kunio; Iwamoto, Naoki; Kawakami, Atsushi; Aoki, Yoshiharu; Takada, Hidetoshi; Ohga, Shoichi; Hasegawa, Shunji.

In: Clinical Rheumatology, Vol. 38, No. 3, 14.03.2019, p. 943-948.

Research output: Contribution to journalArticle

Iida, Y, Wakiguchi, H, Okazaki, F, Nakamura, T, Yasudo, H, Kubo, M, Sugahara, K, Yamashita, H, Suehiro, Y, Okayama, N, Hashimoto, K, Iwamoto, N, Kawakami, A, Aoki, Y, Takada, H, Ohga, S & Hasegawa, S 2019, 'Early canakinumab therapy for the sensorineural deafness in a family with Muckle-Wells syndrome due to a novel mutation of NLRP3 gene', Clinical Rheumatology, vol. 38, no. 3, pp. 943-948. https://doi.org/10.1007/s10067-018-4331-8
Iida, Yasunori ; Wakiguchi, Hiroyuki ; Okazaki, Fumiko ; Nakamura, Tamaki ; Yasudo, Hiroki ; Kubo, Makoto ; Sugahara, Kazuma ; Yamashita, Hiroshi ; Suehiro, Yutaka ; Okayama, Naoko ; Hashimoto, Kunio ; Iwamoto, Naoki ; Kawakami, Atsushi ; Aoki, Yoshiharu ; Takada, Hidetoshi ; Ohga, Shoichi ; Hasegawa, Shunji. / Early canakinumab therapy for the sensorineural deafness in a family with Muckle-Wells syndrome due to a novel mutation of NLRP3 gene. In: Clinical Rheumatology. 2019 ; Vol. 38, No. 3. pp. 943-948.
@article{f3a54659f5a24794bb384751a074decc,
title = "Early canakinumab therapy for the sensorineural deafness in a family with Muckle-Wells syndrome due to a novel mutation of NLRP3 gene",
abstract = "Cryopyrin-associated periodic syndrome (CAPS) is one of the autoinflammatory disorders caused by mutations in NLRP3 gene. The over-production of interleukin (IL)-1β induced by NLRP3 gene mutations plays an important role in the pathophysiology of CAPS. We diagnosed 3 patients with CAPS, who were lineal family members having a novel mutation of NLRP3 gene. The objective of this report is to compare the characteristics of symptoms and differences in the therapeutic responses of them, who had the same mutation. In addition, we aimed to examine the usefulness of cytokine measurement for diagnosis or determination of treatment effect of CAPS. A 5-year-old Japanese boy (proband) came to our hospital because of short stature, reached the diagnosis of Muckle-Wells syndrome (MWS) due to a mutation in NLRP3 gene, which had not been reported so far (p.G328E, c.G983A). His mother and grandmother harbored the same mutation of NLRP3. We measured serum concentrations of cytokines in the proband assessed by flow-cytometric bead array. All of them had episodic skin eruptions with conjunctivitis, hearing loss, and arthralgia, but not periodic fever, cold-triggered episodes, and chronic aseptic meningitis. Only the proband had short stature. Canakinumab therapy led to a prompt relief of symptoms and normalized laboratory data in all patients. Audiograms demonstrated an improved hearing level in the proband, but not two others despite of the same mutation. All cytokines did not show any characteristic findings. Sensorineural hearing loss and itchless rash but not serum cytokine profile deserved attention to the diagnosis and treatment start of CAPS. The early intervention of IL-1β blockade may reduce the chance of complete deafness in patients with CAPS.",
author = "Yasunori Iida and Hiroyuki Wakiguchi and Fumiko Okazaki and Tamaki Nakamura and Hiroki Yasudo and Makoto Kubo and Kazuma Sugahara and Hiroshi Yamashita and Yutaka Suehiro and Naoko Okayama and Kunio Hashimoto and Naoki Iwamoto and Atsushi Kawakami and Yoshiharu Aoki and Hidetoshi Takada and Shoichi Ohga and Shunji Hasegawa",
year = "2019",
month = "3",
day = "14",
doi = "10.1007/s10067-018-4331-8",
language = "English",
volume = "38",
pages = "943--948",
journal = "Clinical Rheumatology",
issn = "0770-3198",
publisher = "Springer London",
number = "3",

}

TY - JOUR

T1 - Early canakinumab therapy for the sensorineural deafness in a family with Muckle-Wells syndrome due to a novel mutation of NLRP3 gene

AU - Iida, Yasunori

AU - Wakiguchi, Hiroyuki

AU - Okazaki, Fumiko

AU - Nakamura, Tamaki

AU - Yasudo, Hiroki

AU - Kubo, Makoto

AU - Sugahara, Kazuma

AU - Yamashita, Hiroshi

AU - Suehiro, Yutaka

AU - Okayama, Naoko

AU - Hashimoto, Kunio

AU - Iwamoto, Naoki

AU - Kawakami, Atsushi

AU - Aoki, Yoshiharu

AU - Takada, Hidetoshi

AU - Ohga, Shoichi

AU - Hasegawa, Shunji

PY - 2019/3/14

Y1 - 2019/3/14

N2 - Cryopyrin-associated periodic syndrome (CAPS) is one of the autoinflammatory disorders caused by mutations in NLRP3 gene. The over-production of interleukin (IL)-1β induced by NLRP3 gene mutations plays an important role in the pathophysiology of CAPS. We diagnosed 3 patients with CAPS, who were lineal family members having a novel mutation of NLRP3 gene. The objective of this report is to compare the characteristics of symptoms and differences in the therapeutic responses of them, who had the same mutation. In addition, we aimed to examine the usefulness of cytokine measurement for diagnosis or determination of treatment effect of CAPS. A 5-year-old Japanese boy (proband) came to our hospital because of short stature, reached the diagnosis of Muckle-Wells syndrome (MWS) due to a mutation in NLRP3 gene, which had not been reported so far (p.G328E, c.G983A). His mother and grandmother harbored the same mutation of NLRP3. We measured serum concentrations of cytokines in the proband assessed by flow-cytometric bead array. All of them had episodic skin eruptions with conjunctivitis, hearing loss, and arthralgia, but not periodic fever, cold-triggered episodes, and chronic aseptic meningitis. Only the proband had short stature. Canakinumab therapy led to a prompt relief of symptoms and normalized laboratory data in all patients. Audiograms demonstrated an improved hearing level in the proband, but not two others despite of the same mutation. All cytokines did not show any characteristic findings. Sensorineural hearing loss and itchless rash but not serum cytokine profile deserved attention to the diagnosis and treatment start of CAPS. The early intervention of IL-1β blockade may reduce the chance of complete deafness in patients with CAPS.

AB - Cryopyrin-associated periodic syndrome (CAPS) is one of the autoinflammatory disorders caused by mutations in NLRP3 gene. The over-production of interleukin (IL)-1β induced by NLRP3 gene mutations plays an important role in the pathophysiology of CAPS. We diagnosed 3 patients with CAPS, who were lineal family members having a novel mutation of NLRP3 gene. The objective of this report is to compare the characteristics of symptoms and differences in the therapeutic responses of them, who had the same mutation. In addition, we aimed to examine the usefulness of cytokine measurement for diagnosis or determination of treatment effect of CAPS. A 5-year-old Japanese boy (proband) came to our hospital because of short stature, reached the diagnosis of Muckle-Wells syndrome (MWS) due to a mutation in NLRP3 gene, which had not been reported so far (p.G328E, c.G983A). His mother and grandmother harbored the same mutation of NLRP3. We measured serum concentrations of cytokines in the proband assessed by flow-cytometric bead array. All of them had episodic skin eruptions with conjunctivitis, hearing loss, and arthralgia, but not periodic fever, cold-triggered episodes, and chronic aseptic meningitis. Only the proband had short stature. Canakinumab therapy led to a prompt relief of symptoms and normalized laboratory data in all patients. Audiograms demonstrated an improved hearing level in the proband, but not two others despite of the same mutation. All cytokines did not show any characteristic findings. Sensorineural hearing loss and itchless rash but not serum cytokine profile deserved attention to the diagnosis and treatment start of CAPS. The early intervention of IL-1β blockade may reduce the chance of complete deafness in patients with CAPS.

UR - http://www.scopus.com/inward/record.url?scp=85055498765&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85055498765&partnerID=8YFLogxK

U2 - 10.1007/s10067-018-4331-8

DO - 10.1007/s10067-018-4331-8

M3 - Article

C2 - 30338413

AN - SCOPUS:85055498765

VL - 38

SP - 943

EP - 948

JO - Clinical Rheumatology

JF - Clinical Rheumatology

SN - 0770-3198

IS - 3

ER -