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Brief Report
October 19, 2016

Pityriasis Rubra Pilaris Type V as an Autoinflammatory Disease by CARD14 Mutations

Author Affiliations
  • 1Department of Dermatology, Nagoya University Graduate School of Medicine, Nagoya, Japan
  • 2St John’s Institute of Dermatology, King’s College London, Guy’s Hospital, London, England
  • 3Department of Dermatology, Hokkaido University Graduate School of Medicine, Sapporo, Japan
  • 4Sakamoto Clinic, Fujieda, Japan
  • 5Faculty of Medicine, Department of Dermatology, Kinki University, Osaka-Sayama, Japan
  • 6Division of Dermatology, Ogikubo Hospital, Tokyo, Japan
  • 7Department of Dermatology, Fujisaki Hospital, Saga, Japan
  • 8Joy Dermatological Clinic, Yamaguchi, Japan
  • 9Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan
  • 10Department of Dermatology, Kawasaki Hospital, Kawasaki Medical School, Okayama, Japan
  • 11Department of Dermatology, Kochi Medical School, Kochi University, Nankoku, Japan
  • 12Department of Dermatology, Faculty of Medicine, Oita University, Yufu, Japan
  • 13Department of Dermatology, Asahikawa Medical University, Asahikawa, Japan
  • 14Department of Dermatology, Juntendo University Urayasu Hospital, Urayasu, Japan
JAMA Dermatol. Published online October 19, 2016. doi:10.1001/jamadermatol.2016.3601
Key Points

Question  Which clinical subtype of patients with pityriasis rubra pilaris (PRP) have pathogenic mutations in CARD14?

Findings  In a case series of 22 cases with varying subtypes of PRP, 3patients with PRP type V were found to have CARD14 mutations.

Meaning  Pityriasis rubra pilaris type V is a distinct variant of PRP that is caused by CARD14 mutations, and a rare variant of CARD14 might also be implicated in the pathophysiology of other forms of PRP.

Abstract

Importance  We found CARD14 mutations (2 de novo novel mutations and another previously reported mutation) in 3 of 3 patients with pityriasis rubra pilaris (PRP) type V, but not in patients with PRP of other types. Our findings, combined with the published literature, suggest that type V PRP, both familial and sporadic, can be caused by CARD14 mutations. Detailed clinical observation revealed that all 3 patients displayed unique patchy macular brown hyperpigmentation.

Objective  To further determine how often patients with PRP have pathogenic mutations in CARD14 and to elucidate which clinical subtype of PRP is caused by CARD14 mutations.

Design, Setting, and Participants  We sequenced the entire coding regions of CARD14 in genomic DNA from patients with 5 clinical subtypes of PRP. The detailed clinical features were analyzed in all the patients. The pathogenicity of each mutation was evaluated by several computational predictions. PRP was classified into 6 subgroups, types I to VI, based on clinical criteria. We categorized all the patients with PRP into the clinical subtypes using the classic PRP classification; 22 cases of PRP with varying subtypes were studied.

Main Outcomes and Measures  The prevalence of CARD14 mutations in each subtype of PRP was evaluated. Clinical features and characteristics of patients with PRP with CARD14 mutations were analyzed.

Results  Overall 22 patients with PRP were included in our study (12 men, 10 women; mean [SD] age, 26 [18] years). Among 3 patients with PRP type V, all were found to have CARD14 mutations: 2 de novo novel mutations (p.Cys127Ser and p.Gln136Leu), and another previously reported mutation (p.Gly117Ser). All were close to the reported pathogenic domains. In silico analysis of all 3 mutations suggested that they are functionally relevant to pathogenesis. All 3 patients displayed unique patchy macular brown hyperpigmentation additionally to other typical features of PRP. Patients with PRP type I and type IV, 1 patient each, had the rare variants in CARD14.

Conclusions and Relevance  Pityriasis rubra pilaris type V is a distinct variant of PRP that is caused by CARD14 mutations. In addition, a rare variant of CARD14 might also be implicated in the pathophysiology of other forms of PRP.

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