Sirolimus treatment for neonate with blue rubber bleb nevus syndrome: A case report

Abstract

BACKGROUND Blue rubber bleb naevus syndrome (BRBNS) is a rare disease that usually presents with multiple venous malformations in the skin and gastrointestinal tract. Lesions located in the gastrointestinal tract always result in chronic gastrointestinal bleeding and severe anemia. The successful management of BRBNS with sirolimus had been reported in many institutions, due to its impact on signaling pathways of angiogenesis. However, the experience in treatment of neonates with BRBNS was limited. CASE SUMMARY A 38-day-old premature female infant born with multiple skin lesions, presented to our center complaining of severe anemia and hematochezia. Laboratory examination demonstrated that hemoglobin was 5.3 g/dL and contrast-enhanced abdominal computed tomography showed multiple low-density space-occupying lesions in the right lobe of the liver. She was diagnosed as having BRBNS based on typical clinical and examination findings. The patient was treated by transfusions twice and hemostatic drugs but symptoms of anemia were difficult to alleviate. A review of BRBNS case reports found that patients had been successfully treated with sirolimus. Then the patient was treated with sirolimus at an average dose of 0.95 mg/m 2 /d with a target drug level of 10-15 ng/mL. During 28 mo of treatment, the lesion was reduced, hemoglobin returned to normal, and there were no adverse drug reactions. CONCLUSION This case highlights the dosing regimen and plasma concentration in neonates, for the current common empiric dose is high.

Case report: Blue rubber bleb nevus syndrome with Kasabach-Merritt phenomenon in a neonate

“…Low-dose sirolimus also has a better therapeutic effect on BRBNS, which can significantly reduce the size of the lesions ( 18 ), and it is also used in neonates ( 4 ). Immunohistochemistry of this patient suggested m-TOR (+).…”

“…The disease was first described in 1,860 by Gascoyen ( 2 ), and then Bean systematically described and named it in 1958, so it is also called Bean syndrome ( 3 ). Sirolimus is a new drug for the treatment of BRBNS, that has a good therapeutic effect and can be administered to neonates ( 4 ).…”

Sirolimus for management of GI bleeding in blue rubber bleb nevus syndrome: A case series

“…32 Sirolimus blocks mTOR, thereby serving as a targeted therapy for BRBNS. Its efficacy was first demonstrated in 2012 31 and since then there have been multiple reports describing its use [12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31] (Table S1).…”

“…Steroids, interferon α‐2a, propranolol, and thalidomide have not demonstrated efficacy and exhibit unfavorable side effects 9–11 . Sirolimus has anti‐angiogenic properties, with multiple reports documenting its success in BRBNS 12–31 . To date, one prospective study exists reporting the efficacy and safety of sirolimus in BRBNS, 12 though questions remain regarding dosing, duration, and long‐term side effects.…”

“…[9][10][11] Sirolimus has antiangiogenic properties, with multiple reports documenting its success in BRBNS. [12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31] To date, one prospective study exists reporting the efficacy and safety of sirolimus in BRBNS, 12 though questions Abbreviations: BRBNS, blue rubber bleb nevus syndrome; CT, computed tomography; EGD, esophagogastroduodenoscopy; GI, gastrointestinal. remain regarding dosing, duration, and long-term side effects.…”