PHACE syndrome with unnoticeable skin lesion and rare anomaly of coronary artery

Abstract

A 4.5-month-old boy had three episodes of respiratory failure from the age of 2.5 months. Plain computed tomography (CT) and magnetic resonance imaging (MRI) showed some fluidfilled cystic lesions around the neck, similar to lymphangioma. At 4.5 months old, he was transferred to Shizuoka Children’s Hospital for the management of airway, presenting stridor, labored breathing, and oxygen desaturation during crying. Although he did not have any skin disorder (Fig. 1a), contrastenhanced CT and bronchoscopy showed a large hemangioma extending from the posterior of the head to the subglottis (Fig. 1b–d). The diameter was > 6 cm, and the subglottic hemangioma occupied approximately 50% of the airway. After oral beta-blocker (propranolol) was started, the airway symptoms gradually resolved in a few days. The dose of propranolol was increased from 1 mg/kg/day to 3 mg/kg/day for 3 days. Given that CT also suggested the possibility of abnormal carotid artery, some additional examinations were performed, such as MRI angiography, ocular examination, hearing test, echocardiography, and blood test for thyroid functions. Consequently, hypoplasia of the left internal carotid artery (ICA) and anomalous origin of the right coronary artery (AORCA) from the left sinus of Valsalva were diagnosed (Fig. 1e,f). Finally, we diagnosed posterior fossa anomalies, hemangioma, arterial lesions, cardiac abnormalities/coarctation of the aorta, eye anomalies (PHACE) syndrome without any apparent skin hemangioma. On day 18, he left hospital. After leaving hospital, his course was uneventful. At 1 year of age the patient underwent follow up. Contrastenhanced CT indicated remarkable reduction of the hemangioma from head to neck (Fig. 1g,h), and on bronchoscopy the subglottic hemangioma was remarkably involuted (Fig. 1i). There was no significant change, however, in the skin appearance of the neck, hypoplasia of the left ICA on MRI, or AORCA on echocardiogram. The dose of propranolol was gradually decreased, and stopped 2 months later. The PHACE syndrome is characterized by large infantile hemangioma (IH) of the face, neck, or scalp associated with developmental defects. Diagnostic criteria were first proposed in 2009, and revised in 2016. The present case met the revised criteria for PHACE syndrome (hemangioma >5 cm in diameter in the head; and another major criterion, anomaly of a major cervical artery), additionally presenting atypical features. In the present case, it was considerably difficult to diagnose the IH, mainly because the skin findings were trivial, even though the patient had a subcutaneously spreading hemangioma at the neck. Finally, contrast-enhanced CT and bronchoscopy under general anesthesia were necessary for diagnosis. PHACE syndrome without apparent skin hemangioma as an atypical feature has been reported previously, but the rate of occurrence of that presentation in PHACE syndrome remains unclear. Although propranolol is considerably effective for IH, it can, rarely, cause acute ischemic stroke in patients with arterial abnormality of the brain. Therefore, in those situations, the beta-blocker should be slowly increased, and the daily dose should be divided into three doses, in order to prevent the blood concentration from fluctuating rapidly. There is no consensus, however, on the optimal time to increase the dosage. In the present case, the dose of propranolol was increased relatively quickly because the airway symptoms needed to be treated immediately. We closely monitored the symptoms in the intensive care unit after initiation of propranolol. To the best of our knowledge, this is the first report of AORCA from the left sinus of Valsalva combined with PHACE syndrome. This anomaly is generally considered more benign, compared with the other type of anomalous coronary artery from the opposite sinus. It is likely, however, to be involved with syncope or, at worst, sudden death in pediatric patients during crying or physical exertion. In this context, this anomaly should be monitored over the patient’s lifetime, and if any symptoms occur in the future, surgical intervention should then be considered. In conclusion, we encountered a case of PHACE syndrome with atypical features. Clinicians should be aware that PHACE syndrome can present without obvious skin hemangioma, and with asymptomatic cardiac anomaly. Correspondence: Akinori Sekioka, MD, Department of Pediatric Surgery, Shizuoka Children’s Hospital, 860 Urushiyama, Aoi-ku, Shizuoka City, Shizuoka 420-8660, Japan. Email: [email protected] Received 10 November 2018; revised 6 January 2019; accepted 14 March 2019. doi: 10.1111/ped.13841