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Sirolimus for diffuse intestinal infantile hemangioma with PHACE features: systematic review



We report a 3-month-old female with cardiovascular anomalies and diffuse intestinal infantile hemangioma (IIH) of the small bowel suggesting possible diagnosis of PHACE syndrome (posterior fossa anomalies, hemangioma, arterial lesions, cardiac abnormalities/coarctation of the aorta, eye anomalies). The GI symptoms persisted under treatment with propranolol, whereas the addition of sirolimus led to regression of the IIH.


A systematic review was conducted using PubMed, EMBASE, and Ovid MEDLINE databases between 1982 and 2021.


A total of 4933 articles were identified; 24 articles met inclusion criteria with 46 IIH cases. The most common GI presentations were unspecified GI bleed (40%) and anemia (38%). The most common treatments were corticosteroids (63%), surgical resection (32.6%), and propranolol (28%). Available outcomes were primarily bleeding arrest (84%). Nine cases (19.5%) were diagnosed with definite PHACE, 5 (11%) with possible PHACE, and 32 (69.5%) no PHACE. Our case presented with symptoms most consistent with those of possible PHACE and definite PHACE. No cases in this review underwent treatment with sirolimus.


This is the first reported case of successful treatment of IIH with sirolimus. Our case, along with other patients who present with IIH and PHACE features, suggests consideration of IIH as a diagnostic criterion for PHACE syndrome.


  • This is the first reported case in which sirolimus showed regression of an intestinal infantile hemangioma.

  • This study serves to demonstrate the presentation, treatment, outcomes of intestinal infantile hemangioma, and correlation with PHACE.

  • The potential correlation between intestinal infantile hemangioma and PHACE deserves more study in consideration of intestinal infantile hemangioma as a diagnostic criterion of PHACE.

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Fig. 1: Diagnostic MRI of our 3-month-old patient's intestinal hemangioma prior to treatment.
Fig. 2: PRISMA search strategy.

Data availability

The dataset generated and analyzed in this study are included in Tables 2 and 3 of this published article with appropriate citations to the original articles.


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We would like to acknowledge Tali Mualem, MD in management of this patient.

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Correspondence to Elana P. Kleinman.

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Kleinman, E.P., Blei, F., Adams, D. et al. Sirolimus for diffuse intestinal infantile hemangioma with PHACE features: systematic review. Pediatr Res (2022).

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