Response of Blue Rubber Bleb Nevus Syndrome to Sirolimus Treatment.
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.



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.



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.



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.
Division of Oncology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio. ralph.salloum@cchmc.org.
Ralph
R
Salloum
Hemangioma and Vascular Malformation Center, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
Courtney E
CE
Fox
Children's Hospital, Calgary, Alberta.
Carlos R
CR
Alvarez-Allende
Division of Oncology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.|Hemangioma and Vascular Malformation Center, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
Adrienne M
AM
Hammill
Division of Pediatric General and Thoracic Surgery, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
Roshni
R
Dasgupta
Division of Pediatric General and Thoracic Surgery, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
Belinda H
BH
Dickie
Division of Oncology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
Paula
P
Mobberley-Schuman
Division of Oncology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
Mary Sue
MS
Wentzel
Division of Oncology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.|Hemangioma and Vascular Malformation Center, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
Carol
C
Chute
Division of Gastroenterology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
Ajay
A
Kaul
Department of Radiology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
Manish
M
Patel
Department of Radiology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
Arnold C
AC
Merrow
Division of Pathology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
Anita
A
Gupta
Division of Gastroenterology, Le Bonheur Children's Hospital, The University of Tennessee Health Science Center, Memphis, Tennessee.
John R
JR
Whitworth
Vascular Anomalies Center, Boston Children's Hospital, Boston, Massachusetts.
Denise M
DM
Adams
D000293:Adolescent; D000903:Antibiotics, Antineoplastic / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D005260:Female; D005770:Gastrointestinal Neoplasms / Q000188:drug therapy* / Q000523:psychology; D006801:Humans; D008297:Male; D018329:Nevus, Blue / Q000188:drug therapy* / Q000523:psychology; D011788:Quality of Life; D012189:Retrospective Studies; D020123:Sirolimus / Q000009:adverse effects / Q000627:therapeutic use*; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000523:psychology
D000903:Antibiotics, Antineoplastic; D020123:Sirolimus
Blue rubber bleb nevus syndrome; rapamycin; sirolimus; vascular malformations