IMPORTANCEWe 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 PARTICIPANTSWe 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 MEASURESThe prevalence of CARD14 mutations in each subtype of PRP was evaluated. Clinical features and characteristics of patients with PRP with CARD14 mutations were analyzed. RESULTSOverall 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.

In addition to the Japanese baseline allergen series version 2008,11 we used cysteamine HCl 1% and 0.5% pet. (Table S1). We also included the participants' own perming solutions, as used by them at the salon, for open tests. RESULTSDetails of the 3 male and 4 female hairdressers, ranging in age from 22 to 73 years, are shown in Table S2. Regarding the cysteamine HCl patch tests, 5 patients showed positive reactions to both 1% and 0.5%. One patient showed a positive reaction to 1% alone, and the other patient, who had a positive reaction to 0.5%, had not been tested with 1% (Table 1). The results of the open test showed that, among 6 patients tested with the reducing agent of the permanent wave products, 5 showed erythema, partly oedema, or papules. Moreover, 6 patients also showed strong positive reactions to components of oxidative hair dye products and related substances. On the other hand, none of the 7 patients showed a positive reaction to ammonium thioglycolate. DISCUSSIONThe active chemicals used to create permanent waves are salts and esters of thioglycolic acid, L-cysteine, and cysteamine HCl. Contact dermatitis caused by cysteamine HCl is reportedly rare, and all cases were related to occupational use. 8,9 On the other hand, Tanita et al reported that 18.8% of 48 hairdressers showed positive patch test reactions to cysteamine 1% pet.in Japan. 12 In a Japanese multicentre study, 10 4.5% of patients (6/132) showed positive patch test reactions to cysteamine HCl 0.5% pet., and 12.6% (24/191) showed positive patch test reactions to cysteamine HCl 1% pet. Although 1% cysteamine HCl had exclusively been used for patch testing, the multicentre study showed that 1% cysteamine HCl may cause false-positive reactions, so a 0.5% concentration was regarded as being more suitable. 10

Stearyl alcohol is found in various cosmetics and topical medications and is regarded as safe. Allergic contact dermatitis is reported due to this chemical on rare occasions. We report seven cases, comprising three men and four women aged between 36 and 62 between the years 2013 to 2019, of allergic contact dermatitis due to the use of topical medication, where the patient showed a positive result to a patch test using stearyl alcohol. There were 10 topical medications that we considered to be the cause of this: three were from Oronine® H ointment, two from Eurax® cream, one from Eurax H cream, and four from topical antifungal medications. All these medications contained stearyl alcohol. Seven cases of patch tests with stearyl alcohol all showed positive results. Moreover, having done a patch test with cetyl alcohol, two out of three tests showed positive. When researching allergic contact dermatitis due to topical medications, it is important to test for allergy to stearyl alcohol as well as their main ingredients, because it is contained in numerous products and has the ability to cause allergic contact dermatitis.

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