Similar Molecular Features in Two Cases of CARD14-Associated Papulosquamous Eruption

Subjects carrying variants in the caspase recruitment domain family member 14 (CARD14) gene can exhibit characteristics of psoriasis and pityriasis rubra pilaris (PRP). The term 'CARD14-associated papulosquamous eruption (CAPE)' is used to describe individuals presenting with symptoms of both conditions. This study aimed to diagnose two cases of CAPE and explore the pathogenic mechanisms, including inflammatory trends and differential features. Whole-exome sequencing and Sanger sequencing identified a novel variant, c.2768T>C and a recurrent variant, c.467T>C, in CARD14 in two unrelated individuals, both exhibiting incomplete penetrance. Both of patients exhibited increased IL-17A in skin lesions, but not in serum, potentially explaining the reported cases with low response rate to secukinumab. One patient also exhibited increased IL-23A in serum. Additionally, the epidermis of lesions showed aberrant late differentiation and active NF-κB signalling.