CARD14 – Associated Papulosquamous Eruption L44.0

Craiglow et al. 2018

CARD14-associated autosomal dominant papulosquamous eruption (CAPE) was first described as a distinct entity in 2018 by Craiglow et al. It typically appears as early as 1 year of age and clinically exhibits characteristics of both psoriasis and pityriasis rubra pilaris. Erythrodermic courses are not rare. In the classifications of pityriasis rubra pilaris, this clinical picture is called "atypical juvenile type" (type V), which occurs in 5% of cases in the overall collective of pityriasis rubra pilaris.

Gain-of-function mutations of CARD14.
Murine gain-of-function mutations in CARD14 ((MIM 697211) enhance the IL-17A-mediatedinflammatory response of keratinocytes (Bertin J et al 2001). CARD-14 mutations have been independently demonstrated with familial and nonfamilial forms of psoriasis, including pustular psoriasis and psoriasis associated with arthritis (Jordan CT et al. 2012a; Jordan CT et al. 2012b), and in type V pityriasis rubra pilaris (familial pityriasis rubra pilaris/Fuchs-Telem D et al. 2012).

First manifestation already in the 1st year of life

The skin phenotype ranges from predominantly "psoriasis-like" to predominantly "pityriasis rubra pilaris-like," with patients also exhibiting features of both diseases. The occurrence of erythroderma is not uncommon. Characteristic is a pronounced facial involvement, which is already detectable in the early course of the disease. Symmetrical, pink spots or little infiltrated, blurred plaques are found. Involvement of the trunk and extremities is variable. Nappes claires can often be detected. Follicular, rub-like accentuation is possible. Palmoplantar keratoses are regularly found (characteristic of pityriasis rubra pilaris); scleroderma-like indurations of both hands are less common.

Psoriasiform dermatitis with lamellar orthohyperkeratosis, parakeratosis areas, psoriasiform elongation of the rice ridges, and a subepidermal perivascular lymphocytic infiltrate with evidence of intraepidermal neutrophil granulocytes.

Immunohistochemistry: Immune cell infiltrate consisting of dendritic cells (CD11c) and T cells (CD4, CD8). The proliferation marker MIB1 is present in several suprabasal cell layers in contrast to healthy controls (sign of epidermal hyperproliferation).

The diagnosis is made after receipt of the genetic findings, taking into account the clinical picture.

Arthritic changes can be detected in about 20% of patients.

Patients respond poorly to topical medications such as corticosteroids, calcineurin inhibitors, vitamin D analogs, topical retinoids. Response to other treatments, including phototherapy, oral retinoids, methotrexate, cyclosporine is variable. Etanercept as monotherapy is poorly successful.

Good response to ustekinumab. As an inhibitor targeting cytokines IL-12 and IL-23 by binding to their common p40 subunit18,19, ustekinumab is a pathogenesis-based treatment for CAPE.

Alternative: ixekizumab: Sporadic response ixekizumab has also been reported (Klein B et al. 2023). Therefore, inhibition of the IL-17A-CARD14 signaling loop could potentially inhibit cytokines other than immune mediators.

Alternative: Guselkumab, an IL-23p19 inhibitor recently approved for the treatment of plaque psoriasis, represents another potential pathogenesis-based treatment for this patient population.

Alternative: Secukinumab (IL-17A inhibitor).

CARD14 mutations are independently associated with psoriasis and familial PRP4 and provide a pathophysiological link between these diseases. The early age of onset and chronicity of the disease are consistent with atypical juvenile pityriasis rubra pilaris.

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