Response of Blue Rubber Bleb Nevus Syndrome to Sirolimus Treatment

Pediatr Blood Cancer. 2016 Nov;63(11):1911-4. doi: 10.1002/pbc.26049. Epub 2016 Jun 8.


Background: Blue rubber bleb nevus syndrome (BRBNS) is a rare multifocal venous malformation syndrome involving predominantly the skin and gastrointestinal tract. Traditional treatment modalities include corticosteroids, interferon-α, sclerotherapy, and aggressive surgical resection. Sirolimus has been used in several single case reports.

Procedure: We performed a single-institution retrospective review of four children with BRBNS, who received sirolimus as part of their treatment regimens. A diagnosis of BRBNS was based on clinical, radiologic, and pathologic criteria.

Results: Median age was 6.5 years (range: 2-16 years). Pathologic evaluations revealed a combined malformation with venous and lymphatic components. The novel finding of a lymphatic component was confirmed with PROX-1 immunostaining. Patients received oral sirolimus with target drug levels between 10 and 13 ng/ml. Responses to treatment were defined as stabilization/decrease in size of lesions; resolution of transfusion requirements; reduction in pain, and improvement in quality of life (QOL). Median time to response was 1.5 months (SD ± 0.96 month, range: 1-3 months). Median follow-up was 21 months (range: 18-26 months). Lesion size and characteristics improved in all patients. All patients reported decrease in pain and improvement in QOL. All three patients requiring transfusions became transfusion-independent. One patient had resolution of coagulopathy. Adverse effects of sirolimus consisted of mucositis in three patients and neutropenia in one patient.

Conclusions: Sirolimus is safe and efficient for the treatment of BRBNS. Further prospective studies are needed to evaluate the long-term effectiveness of this drug. This is the first report that identifies a lymphatic component as part of BRBNS.

Keywords: Blue rubber bleb nevus syndrome; rapamycin; sirolimus; vascular malformations.

MeSH terms

  • Adolescent
  • Antibiotics, Antineoplastic / therapeutic use*
  • Child
  • Child, Preschool
  • Female
  • Gastrointestinal Neoplasms / drug therapy*
  • Gastrointestinal Neoplasms / psychology
  • Humans
  • Male
  • Nevus, Blue / drug therapy*
  • Nevus, Blue / psychology
  • Quality of Life
  • Retrospective Studies
  • Sirolimus / adverse effects
  • Sirolimus / therapeutic use*
  • Skin Neoplasms / drug therapy*
  • Skin Neoplasms / psychology


  • Antibiotics, Antineoplastic
  • Sirolimus

Supplementary concepts

  • Blue rubber bleb nevus syndrome