Unilateral Nevoid Telangiectasia in a Healthy Man.

We report the case of a healthy 26-year-old man presenting telangiectatic macules on the left thorax and arm since childhood. The main diagnostic hypothesis were unilateral nevoid telangiectasia (UNT), hereditary benign telangiectasia, atrial myxoma, segmental serpiginous angioma, circumscribed neviform angiokeratoma, and nevus vascularis mixtus. The diagnosis retained was UNT characterized by congenital or acquired telangiectasia distributed asymmetrically along the upper extremities, or the third or fourth cervical dermatomes. The congenital form is extremely rare, predominant in men, and persists in adulthood. The acquired form is most frequent, affects preferentially women, usually appears at puberty or during pregnancy and tends to disappear. Estrogen excess triggers the formation of telangiectasia. UNT is rarely associated with liver or thyroid disorder. Pulsed-dye lasers and normalization of estrogen are proposed as therapeutic options. We report a rare diagnosis of UNT in a young man with no other underlying condition. We would like to highlight that in the presence of unilateral telangiectasia, a complete clinical examination must be performed to rule out signs of hyperestrogenism in man, ocular or neurological abnormalities, a blood test to exclude pregnancy, hepatic and thyroid dysfunctions, and ultrasonography in case of suspicion of atrial myxoma.

Characterization of CYP26B1-Selective Inhibitor, DX314, as a Potential Therapeutic for Keratinization Disorders.

Inhibition of CYP450-mediated retinoic acid (RA) metabolism by RA metabolism blocking agents increases endogenous retinoids and is an alternative to retinoid therapy. Currently available RA metabolism blocking agents (i.e., liarozole and talarozole) tend to have fewer adverse effects than traditional retinoids but lack target specificity. Substrate-based inhibitor DX314 has enhanced selectivity for RA-metabolizing enzyme CYP26B1 and may offer an improved treatment option for keratinization disorders such as congenital ichthyosis and Darier disease. In this study, we used RT-qPCR, RNA sequencing, pathway, upstream regulator, and histological analyses to demonstrate that DX314 can potentiate the effects of all-trans-RA in healthy and diseased reconstructed human epidermis. We unexpectedly discovered that DX314, but not all-trans-RA or previous RA metabolism blocking agents, appears to protect epidermal barrier integrity. In addition, DX314-induced keratinization and epidermal proliferation effects are observed in a rhino mice model. Altogether, the results indicate that DX314 inhibits all-trans-RA metabolism with minimal off-target activity and shows therapeutic similarity to topical retinoids in vitro and in vivo. Findings of a barrier-protecting effect require further mechanistic study but may lead to a unique strategy in barrier-reinforcing therapies. DX314 is a promising candidate compound for further study and development in the context of keratinization disorders.