title: Beneficial effect of ustekinumab in familial pityriasis rubra pilaris with a new missense mutation in CARD14.
abstract: Pityriasis rubra pilaris (PRP) represents a group of rare chronic inflammatory skin disorders in which around one 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), which activates the noncanonical nuclear factor (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 patients. A 49-year-old woman and her 20-year-old son had lifelong, generalized, patchy erythematous scale with a few islands of sparing, as well as minor nail ridging and mild palmoplantar keratoderma, features consistent with generalized PRP. Topical steroids, phototherapy and oral retinoids proved ineffective. Following informed consent, Sanger sequencing of CARD14 in both individuals revealed a new heterozygous single-nucleotide transversion in exon 4, c.356T>G, resulting in the missense mutation p.Met119Arg. Ustekinumab, at a dose of 45 mg 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-κB signalling in familial PRP with mutations in CARD14.
authors.affiliation: St John's Institute of Dermatology, King's College London (Guy's Campus), London, U.K.
authors.forename: S M
authors.identifier: 0000-0002-3325-3675
authors.initials: SM
authors.lastname: Lwin
authors.affiliation: St John's Institute of Dermatology, King's College London (Guy's Campus), London, U.K.|Department of Dermatology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
authors.forename: C-K
authors.initials: CK
authors.lastname: Hsu
authors.affiliation: Viapath, St Thomas' Hospital, London, U.K.
authors.forename: L
authors.initials: L
authors.lastname: Liu
authors.affiliation: Department of Dermatology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
authors.forename: H-Y
authors.initials: HY
authors.lastname: Huang
authors.affiliation: Dermatology, Norfolk and Norwich University Hospitals NHS Foundation Trust, Norwich, U.K.
authors.forename: N J
authors.initials: NJ
authors.lastname: Levell
authors.affiliation: St John's Institute of Dermatology, King's College London (Guy's Campus), London, U.K.
authors.forename: J A
authors.initials: JA
authors.lastname: McGrath
mesh_terms: D053468:CARD Signaling Adaptor Proteins / Q000235:genetics*; D003879:Dermatologic Agents / Q000627:therapeutic use*; D005260:Female; D006162:Guanylate Cyclase / Q000235:genetics*; D006801:Humans; D033162:Incidental Findings; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D020125:Mutation, Missense / Q000235:genetics*; D010375:Pedigree; D010916:Pityriasis Rubra Pilaris / Q000188:drug therapy* / Q000235:genetics; D000069549:Ustekinumab / Q000627:therapeutic use*; D055815:Young Adult
chemical_list: D053468:CARD Signaling Adaptor Proteins; D003879:Dermatologic Agents; D008565:Membrane Proteins; C426243:CARD14 protein, human; D006162:Guanylate Cyclase; D000069549:Ustekinumab