Sturge-Weber syndrome (SWS) is a neurocutaneous disorder that classically presents with a triad of vascular anomalies affecting the skin, eyes, and brain. Previously, the trigeminal nerve distribution of a port-wine birthmark (PWB) of the face was used to identify risk of SWS. However, recent evidence has demonstrated that PWBs are vascular, not neurologic, in embryologic origin, and facial PWBs at highest risk for the brain involvement of SWS involve the forehead location. Furthermore, a PWB involving the upper or lower eyelid carries a risk of glaucoma, which requires lifelong monitoring. The gold standard of treatment for PWB is the pulsed dye laser, which has many advantages when started as early as possible in infancy. In this review, we discuss the locations of facial PWBs at risk for neurologic and ophthalmologic complications, the differential diagnosis of facial vascular birthmarks, recommendations for patient referral(s) when needed, and the advantages of early laser therapy when desired for the PWB. We also provide additional resources for pediatricians to support patients and their families.

Background

Heterozygous mutations in caspase recruitment domain family member 14 gene (CARD14) have been shown to be associated with psoriasis and familial pityriasis rubra pilaris (PRP). Many subjects with CARD14 mutations display features of both disorders, which can result in diagnostic uncertainty. In addition, these eruptions are often recalcitrant to conventional psoriasis therapies such as methotrexate, oral retinoids, and tumor necrosis factor-α inhibitors.

Objective

We sought to describe the clinical characteristics, family history, and response to therapy in subjects with papulosquamous eruptions due to mutations in CARD14.

Methods

Subjects were referred for genetic testing as part of a registry of subjects with inherited disorders of keratinization. DNA was isolated from blood or saliva, and multiplex targeted sequencing or whole exome sequencing was performed. Clinical histories of subjects with CARD14 mutations were reviewed.

Results

We identified 15 kindreds with CARD14-associated papulosquamous eruption (CAPE). Characteristic features of CAPE include early age of onset; prominent involvement of the cheeks, chin, and ears; family history of psoriasis or PRP; minimal response to conventional topical and systemic psoriasis therapies; and improvement with ustekinumab.

Limitations

Relatively small sample size.

Conclusions

Many subjects with CARD14 mutations display characteristics of both psoriasis and PRP. We propose the term CARD14-associated papulosquamous eruption to describe this spectrum of disease. Subjects with clinical features suggestive of CAPE should undergo CARD14 sequencing and may benefit from treatment with ustekinumab.