Faculty Bibliography

BACKGROUND: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. METHODS:A systematic review was conducted using PubMed, EMBASE, and Ovid MEDLINE databases between 1982 and 2021. RESULTS: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. CONCLUSIONS: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. IMPACT/CONCLUSIONS: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.

BACKGROUND/OBJECTIVES/OBJECTIVE:The COVID-19 pandemic prompted a rapid expansion in the use of telemedicine. This study aimed to assess the experiences of hemangioma specialists utilizing telemedicine during the COVID-19 pandemic to evaluate and manage infantile hemangiomas (IH), including perceived effectiveness of different modalities and barriers to care delivery. METHODS:Multicenter cross-sectional study asking providers to describe their experiences using telemedicine for initial evaluation of IH from March to September 2020. RESULTS:The study included 281 patients from 15 medical centers internationally. Median time from referral to evaluation was 17 days. Median physician confidence in performing evaluations via telemedicine was 95.0 (IQR 90.0-100.0). Most evaluations were performed via video communication with photographs or audio communication with photographs; when not initially available, photographs were requested in 51.4%. Providers preferred follow-up modalities that included photographs. CONCLUSIONS:Physicians with extensive expertise in managing IH are confident in their abilities to assess and manage IH via telemedicine including initiating treatment in patients without risk factors for beta-blocker therapy. There was a preference for hybrid modalities that included photographs. The data suggest that telemedicine can be effective for managing IH and may decrease wait times and improve specialist reach to underserved areas.

The acronym PHACE (posterior fossa anomalies, infantile hemangiomas, arterial anomalies, cardiac defects and eye anomalies) was coined to describe the features of an uncommon sporadic condition with a vascular tumor (infantile hemangioma), developmental and progressive vascular abnormalities. Here, we report the findings of our analysis of whole genome sequencing of germline samples from 98 unrelated trios in which the probands had PHACE. Two coding variants, RASA3-p.Val85Met and THBS2-p.Asp859Asn, were predicted to be pathogenic by numerous algorithms. This analysis was negative for a shared gene across multiple probands; however, a g:Profiler pathway analysis of the genes with rare, de novo variants demonstrated combinatorial variants in the RAS/MAPK pathway. Coding and noncoding variants in six RAS pathway genes were prioritized based on the vascular abnormalities reported in knockout mouse models. To identify lineages in which the genes may be acting, we explored the expression of the prioritized candidate genes RASA3, AFF2, DLC1, EPHA3, PIK3CA, and THBS2 across diverse cell types in the human developing heart by incorporating chromatin accessibility (scATAC-seq) and gene expression (scRNA-seq) datasets. We observed that AFF2, EPHA3, PIK3CA, and THBS2 are co-expressed in the vascular smooth muscle cells in the fetal heart, whilst AFF2, EPHA3, and PIK3CA are co-expressed in the vascular endothelium. These findings suggest oligogenic variants in RAS pathway genes may contribute to the developmental vascular abnormalities in PHACE.
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