CARD14‐associated papulosquamous eruption (CAPE) in pediatric patients: Three additional cases and review of the literature

Abstract

CARD14‐associated papulosquamous eruption (CAPE) is a proposed term that encompasses features ranging from psoriasis to pityriasis rubra pilaris (PRP) in association with CARD14 mutations. The early onset of the disease, prominent facial involvement, family history of an autosomal dominant trait, and poor response to conventional treatment are characteristics of CAPE that distinguish it from classical psoriasis and PRP. We describe the clinical features, family history, and response to therapy in three unrelated children with CAPE and compare these characteristics with those of previously described pediatric patients. Testing for CARD14 mutations in children with early onset of features of psoriasis or pityriasis rubra pilaris and resistance to conventional therapy should be considered.

Beyond plaque psoriasis – pathogenesis and treatment of other psoriasis phenotypes

“…Most cases are sporadic, but familial cases have been reported in PRP type V, with an autosomal-dominant inheritance pattern [68]. More recently, gain-of-function variants in CARD14 have been detected in PRP type V patients [69,70], leading to reclassification of PRP type V as a distinct entity: CARD14-associated papulosquamous eruption (CAPE) [71]. Clinical features of this disease include early onset of disease (before 1 year of age), prominent facial involvement, family history of psoriasis or PRP and poor response to conventional treatment [71].…”

Tailored treatments in inborn errors of immunity associated with atopy (IEIs-A) with skin involvement

“…The upregulation of CARD14 lead to excessive expression of NF-kBresponsive genes and initiate the recruitment of the inflammatory cells, including dendritic cells and T cells producing IL-23 and IL-17/IL-22 respectively (47). In line with this, ustekinumab, an inhibitor that targets both IL-12 and IL-23 cytokines, proved to be a successful treatment in an increasing numbers of patients with CARD14 GOF mutations (45,(48)(49)(50)(51). Since the role of CARD14 in both AD and psoriatic diseases, targeted therapies in these patients need to be considered with caution.…”

“…CARD14 induces the NF- κ B and mitogen-activated protein kinase (MAPK or MAP kinase) signaling through BCL10 and MALT1, upregulating pro-inflammatory genes. While upregulation of CARD14 gives a skin picture overlapping with psoriasis ( 43 ) and atypical juvenile pityriasis rubra pilaris ( 44 , 45 ), its downregulation is associated with AD, increased risk of skin infection and also dysregulating cutaneous inflammation. Dominant LOF mutations in CARD14 are associated with severe AD, impaired NF-kB cascade, and dysregulation of innate immunity mediators involved in AD pathogenesis ( 46 ).…”

Psoriasis in children and adolescents

“…Für die Psoriasis pustulosa generalisata bilden dagegen Mutationen im IL36RN -Gen die bedeutendste genetische Basis [ 30 ], weswegen diese schwere, autosomal-rezessiv vererbte Erkrankung auch als DITRA (Defizienz des Interleukin-36-Rezeptor-Antagonisten) bezeichnet wird. Autosomal-dominant vererbbare, aktivierende Mutationen im CARD14 -Gen können ebenfalls eine Psoriasis pustulosa verursachen, häufiger jedoch einen als CAPE (CARD-14-assoziierte papulosquamöse Eruption) bezeichneten Phänotyp, der sich in einer frühmanifesten, besonders schwer und chronisch verlaufenden Plaquepsoriasis bis hin zur Psoriasiserythrodermie oder in einer Pityriasis rubra pilaris äußert [ 7 ].…”