Lisa Arkin, MD – University of Wisconsin, Madison
Facial vascular stains affect 0.3-0.5% of newborns; they reduce quality of life due to soft tissue overgrowth, nodularity and life-altering, stigmatizing disfigurement. Laser treatment is the current standard of care and relies on selective destruction of aberrant vessels. Yet up to 50% are refractory to laser, and <25% clear entirely. Optimal laser settings require consideration of vessel diameter and depth. In treating patients, clinicians make a blind guess about these parameters, using the immediate endpoint of purpura as a visual marker for destruction. This endpoint, however, doesn’t guarantee vessel shut down or clearance of the vascular stain. Optical coherence tomography (OCT), which was FDA approved for skin-specific imaging in 2010, is a non-invasive imaging modality that uses multiple laser beams scanned simultaneously to enable rapid, non-invasive characterization of vessel diameter and depth. This novel imaging offers the potential for more precise laser destruction of vessels.
Recently, the genetic etiology of vascular stains has been elucidated. They are caused by mosaic mutations in genes that regulate the cell cycle and lead to tightly regulated cellular proliferation and growth. This discovery has transformed our fundamental understanding of the pathophysiology of these birthmarks. It provides a molecular explanation for the development of laser resistance, as these genes share oncogenic pathways that control cell growth, division and death. This underscores the observed resistance to laser as a single treatment modality, since residual mutated cells that escape complete destruction through photo coagulation will continue to multiply.
This proposal aims to leverage genotyping of vascular stains with deep, paired clinical phenotyping, to inform creation of a targeted laser algorithm. We will exploit existing institutional and Pediatric Dermatology Research Alliance (PeDRA) infrastructure to create a compelling cohort. In Aim 1, we will enroll patients, create a tissue biorepository and perform deep, paired clinical phenotyping including OCT to characterize median vessel diameter and depth. In Aim 2, we will correlate genotype with clinical phenotype, and integrate OCT data to create a targeted, laser algorithm to optimize laser destruction of mutated cells. The goal is to create a formula that could be applied by defining clinical phenotype of the stain – simply by examining the patient.
Upon completion, we will have refined genotype-phenotype correlations enhanced by novel imaging, all of which will accelerate precision-based treatments to prevent disfigurement and improve quality of life.
This study was funded through the 2019 PeDRA Research Hot Seat – A PeDRA Shark Tank.