title: The majority of generalized pustular psoriasis without psoriasis vulgaris is caused by deficiency of interleukin-36 receptor antagonist.
abstract: Generalized pustular psoriasis (GPP) is a rare inflammatory skin disease that can be life-threatening. Recently, it has been reported that familial GPP is caused by homozygous or compound heterozygous mutations of IL36RN. However, the majority of GPP cases are sporadic and it is controversial whether IL36RN mutations are a causative/predisposing factor for sporadic GPP. We searched for IL36RN mutations in two groups of GPP patients in the Japanese population in this study: GPP without psoriasis vulgaris (PV), and GPP with PV. Eleven cases of GPP without PV (GPP alone) and 20 cases of GPP accompanied by PV (GPP with PV) were analyzed. Surprisingly, 9 out of 11 cases of GPP alone had homozygous or compound heterozygous mutations in IL36RN. In contrast, only 2 of 20 cases of GPP with PV had compound heterozygous mutations in IL36RN. The two cases of GPP with PV who had compound heterozygous mutations in IL36RN are siblings, and both cases had PV-susceptible HLA-A*0206. We determined that GPP alone is a distinct subtype of GPP and is etiologically distinguished from GPP with PV, and that the majority of GPP alone is caused by deficiency of the interleukin-36 receptor antagonist due to IL36RN mutations.
authors.affiliation: Department of Dermatology, Nagoya University Graduate School of Medicine, Nagoya, Japan. Electronic address: kazusugi@med.nagoya-u.ac.jp.
authors.forename: Kazumitsu
authors.initials: K
authors.lastname: Sugiura
authors.affiliation: Department of Dermatology, Yamaguchi University Graduate School of Medicine, Yamaguchi, Japan.
authors.forename: Akemi
authors.initials: A
authors.lastname: Takemoto
authors.affiliation: Department of Dermatology, Yamaguchi University Graduate School of Medicine, Yamaguchi, Japan.
authors.forename: Michiya
authors.initials: M
authors.lastname: Yamaguchi
authors.affiliation: Department of Dermatology, Asahikawa Medical University, Asahikawa, Japan.
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Takahashi
authors.affiliation: Department of Dermatology, Sumitomo Hospital, Osaka, Japan.
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Shoda
authors.affiliation: Department of Dermatology, Ichinomiya City Hospital, Ichinomiya, Japan.
authors.forename: Teruyuki
authors.initials: T
authors.lastname: Mitsuma
authors.affiliation: Department of Dermatology, Mie University Graduate School of Medicine, Tsu, Japan.
authors.forename: Kenshiro
authors.initials: K
authors.lastname: Tsuda
authors.affiliation: Department of Dermatology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
authors.forename: Emi
authors.initials: E
authors.lastname: Nishida
authors.affiliation: Department of Dermatology, Chiba University Graduate School of Medicine, Chiba, Japan.
authors.forename: Yaei
authors.initials: Y
authors.lastname: Togawa
authors.affiliation: Department of Dermatology, Kochi Medical School, Kochi University, Kochi, Japan.
authors.forename: Kimiko
authors.initials: K
authors.lastname: Nakajima
authors.affiliation: Department of Dermatology, Anjo Kosei Hospital, Anjo, Japan.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Sakakibara
authors.affiliation: Department of Dermatology, Azumi General Hospital, Kitaazumi, Japan.
authors.forename: Shigeo
authors.initials: S
authors.lastname: Kawachi
authors.affiliation: Department of Dermatology, National Hospital Organization, Nagoya Medical Center, Nagoya, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Shimizu
authors.affiliation: Department of Division for Medical Research Engineering, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Yasutomo
authors.initials: Y
authors.lastname: Ito
authors.affiliation: Department of Dermatology, Nagoya University Graduate School of Medicine, Nagoya, Japan; Department of Dermatology, Inazawa City Hospital, Inazawa, Japan.
authors.forename: Takuya
authors.initials: T
authors.lastname: Takeichi
authors.affiliation: Department of Dermatology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Michihiro
authors.initials: M
authors.lastname: Kono
authors.affiliation: Department of Dermatology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Ogawa
authors.affiliation: Department of Dermatology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Yoshinao
authors.initials: Y
authors.lastname: Muro
authors.affiliation: Department of Dermatology, Asahikawa Medical University, Asahikawa, Japan.
authors.forename: Akemi
authors.initials: A
authors.lastname: Ishida-Yamamoto
authors.affiliation: Department of Dermatology, Kochi Medical School, Kochi University, Kochi, Japan.
authors.forename: Shigetoshi
authors.initials: S
authors.lastname: Sano
authors.affiliation: Department of Dermatology, Chiba University Graduate School of Medicine, Chiba, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Matsue
authors.affiliation: Department of Dermatology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
authors.forename: Akimichi
authors.initials: A
authors.lastname: Morita
authors.affiliation: Department of Dermatology, Mie University Graduate School of Medicine, Tsu, Japan.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Mizutani
authors.affiliation: Department of Dermatology, Asahikawa Medical University, Asahikawa, Japan.
authors.forename: Hajime
authors.initials: H
authors.lastname: Iizuka
authors.affiliation: Department of Dermatology, Yamaguchi University Graduate School of Medicine, Yamaguchi, Japan.
authors.forename: Masahiko
authors.initials: M
authors.lastname: Muto
authors.affiliation: Department of Dermatology, Nagoya University Graduate School of Medicine, Nagoya, Japan. Electronic address: makiyama@med.nagoya-u.ac.jp.
authors.forename: Masashi
authors.initials: M
authors.lastname: Akiyama
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D044466:Asian People / Q000235:genetics*; D002675:Child, Preschool; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006239:Haplotypes; D006579:Heterozygote; D006650:Histocompatibility Testing; D006720:Homozygote; D006801:Humans; D007378:Interleukins / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011565:Psoriasis / Q000235:genetics* / Q000473:pathology*; D055815:Young Adult
chemical_list: C122187:IL36RN protein, human; D007378:Interleukins