Beneficial effect of ustekinumab in familial pityriasis rubra pilaris with a new missense mutation in CARD14

Lwin, S M, Hsu, C-K, Levell, N J and McGrath, J A (2018) Beneficial effect of ustekinumab in familial pityriasis rubra pilaris with a new missense mutation in CARD14. British Journal of Dermatology, 178 (4). pp. 969-972. ISSN 0007-0963

[img]
Preview
PDF (Accepted manuscript) - Submitted Version
Download (212kB) | Preview

Abstract

Pityriasis rubra pilaris (PRP) represents a group of rare chronic inflammatory skin disorders in which ~1 in 20 affected individuals show autosomal dominant inheritance. In such cases, there may be gain-of-function mutations in CARD14, encoding caspase recruitment domain-containing protein 14 (CARD14) that activates the non-canonical nuclear factor-kappa B (NF-κB) pathway, thereby promoting cutaneous inflammation. Here, we report a mother and son with PRP due to a new missense mutation in CARD14 and describe the beneficial clinical effects of ustekinumab, a monoclonal antibody against interleukins-12 and -23, in both subjects. A 49 year-old female and her 20 year-old son had lifelong, generalised, patchy erythematous scale with a few islands of sparing, as well as minor nail ridging and mild palmoplantar keratoderma, features consistent with generalised PRP. Topical steroids, phototherapy and oral retinoids proved ineffective therapies. Following informed consent, Sanger sequencing of CARD14 in both individuals revealed a new heterozygous single nucleotide transversion in exon 16, c.356T>G, resulting in the missense mutation, p.Met119Arg. Ustekinumab, at a dose of 45mg every 12 weeks, brought about a significant physical and emotional improvement in both the mother and son within a few days of the initial dose, which was sustained on maintenance dosing. This report highlights the therapeutic potential of biologics that downregulate NF-kB signalling in familial PRP with mutations in CARD14. This article is protected by copyright. All rights reserved.

Item Type: Article
Additional Information: This article is protected by copyright. All rights reserved.
Faculty \ School: Faculty of Medicine and Health Sciences > Norwich Medical School
Depositing User: Pure Connector
Date Deposited: 30 Mar 2017 00:42
Last Modified: 10 Oct 2019 00:12
URI: https://ueaeprints.uea.ac.uk/id/eprint/63116
DOI: 10.1111/bjd.15462

Actions (login required)

View Item View Item