Clinical characteristics of blue rubber bleb nevus syndrome in adults: systematic scoping review

Blue rubber bleb nevus syndrome (BRBNS) is a rare systemic vascular anomaly mainly affecting the skin, central nervous system and gastrointestinal tracts. Its clinical presentation and characteristics in adult patients are unclear.

To clarify the characteristics of BRBNS in adult patients with a focus on gastrointestinal symptoms.

Following the PRISMA Extension for Scoping Reviews, we searched MEDLINE and EMBASE for all peer-reviewed articles using keywords including 'Blue rubber bleb nevus syndrome' from their inception to 28 December 2021.

Ninety-nine articles, including 3 observational studies and 101 cases from case reports and series, were included. Observational studies were consistently with small sample sizes, and there was only one prospective study to show the effectiveness of sirolimus in BRBNS. Common clinical presentations included anemia (50.5%) and melena (26.5%). While skin findings were known to be representative of BRBNS, only 57.4% had known vascular malformation. The diagnosis was primarily made clinically, with only 1% being diagnosed with BRBNS through genetic sequencing. Distribution of BRBNS-related lesions were variable, but predominantly oral (55.9%), followed by small bowel (49.5%), colorectal (35.6%) and stomach (26.7%) vascular malformations.

While it has been underrecognized, adult BRBNS could be a culprit for refractory microcytic anemia or occult gastrointestinal bleeding. Further studies are critical to establish a uniform understanding of diagnosis and treatment for those with adult BRBNS. The utility of genetic testing in adult BRBNS diagnosis and the patient characteristics that may benefit from sirolimus, a potentially curative agent, remain to be clarified.