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Sirolimus may reduce refractory hemangiomas


mTOR inhibitor helps child with diffuse vascular anomalies and extensive organ involvement.

Although propranolol has quickly become first-line therapy for troublesome infantile hemangiomas (IH), not all children respond to this therapy. A recent case supports a growing body of literature suggesting that sirolimus can help children with complex vascular anomalies.

Researchers led by Kelley K. Hutchins, D.O., M.P.H., of Wayne State University School of Medicine, reported the case of an African-American girl who presented shortly after birth with hepatosplenomegaly and multiple cutaneous hemangiomas displaying different stages of involution. Magnetic resonance imaging/angiography (MRI/A) revealed replacement of the entire liver parenchyma by nodular lesions consistent with IH, and cardiomegaly suggestive of early heart failure. Laboratory tests revealed anemia, prolonged prothrombin time and other problems.

After diagnosing consumptive coagulopathy, physicians treated the patient with propranolol (1 mg/kg every 8 hours) and prednisolone (3 mg/kg/day) for hemangiomas, as well as digoxin, furosemide and spironolactone for high-output cardiac failure. She was discharged at one month of age, with continued propranolol and steroids for her hepatic and cutaneous hemangiomas.

Physicians were able to wean the patient off prednisone and propranolol by around 17 months of age. At around 2 years old, the patient resumed propranolol because MRI showed that her hepatic lesions had grown. She had also developed severe idiopathic pulmonary hypertension (PH).

Because the patient's cutaneous and hepatic lesions improved but never resolved on propranolol, she started sirolimus (0.8 mg/m2 twice daily) at 38 months. In 2 months, her PH improved significantly, as did her hepatic hemangiomas. Angiography showed no evidence of pulmonary arteriovenous malformations, but after the procedure the patient unexpectedly developed severe hypoglycemia that proved fatal. Her pulmonary and hepatic lesions stained positive for glucose transporter isoform 1 (GLUT1), confirming the diagnosis of IH.1

Sirolimus has proven effective for several pediatric cases involving vascular anomalies. By inhibiting the cell cycle regulator mammalian target of rapamycin (mTOR), it is believed to decrease protein synthesis and reduce cell proliferation and angiogenesis.2 Sirolimus also inhibits the self-renewal capacity of IH stem cells.3

"While on sirolimus," the authors wrote, "our patient demonstrated significant radiographic response to her hepatic lesions, and the clinical improvement in her PH suggests improvement in her pulmonary lesions despite autopsy findings which did not show significant involution." Hypoglycemia is a known side effect of propranolol, they added, while sirolimus also has been reported to cause glucose dysregulation. Accordingly, "Children at risk of hypoglycemia should receive dextrose-containing solution or have monitoring of blood glucose levels during the periprocedural period."4

In light of a recent report demonstrating the safety and efficacy of sirolimus in children with complicated vascular anomalies, the authors reasoned, it is unlikely that sirolimus contributed to their patient's demise. Rather, they wrote, her case "further supports the use of this medication in complicated cases with multiorgan involvement."



1. North PE, Waner M, Mizeracki A, et al. GLUT1: a newly discovered immunohistochemical marker for hemangiomas. Hum Pathol. 2000;31:11-22.

2. Hammill AM, Wentzel M, Gupta A, et al. Sirolimus for the treatment of complicated vascular anomalies in children. Pediatr Blood Cancer. 2011;57:1018-1024.

3. Greenberger S, Yuan S, Walsh LA, et al. Rapamycin suppresses self-renewal and vasculogenic potential of stem cells isolated from infantile hemangioma. J Invest Dermatol. 2011;131:2467-2476.

4. Association of Pediatric Anaesthesia. APA consensus guidelines on perioperative fluid management in children. 


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