Wyclif Mukupa1, Mutale Nyaywa2, Funjika Misa1 and Kangwa I. M. Muma3,4
1Department of Ophthalmology, Ndola Teaching Hospital, Ndola, Zambia.
2Arthur Davison Children’s Hospital, Ndola, Zambia.
3Ministry of Health, Lusaka, Zambia
4University Teaching Hospitals – Eye Hospital, Lusaka, Zambia
A 1year 8 months old baby girl presented to Arthur Davidson Children’s Hospital with a 4 month history of segmental haemangioma affecting the Left upper which caused mechanical ptosis obstructing the visual axis, with supraumbilical raphe, sternal cleft defect and ventricular septal defect. The clinical features were consistent with PHACES syndrome. Three monthly doses of intralesional methyl-prednisolone were administered with complete regression of the haemangioma.
Infantile haemangioma (IH) is the most common tumour in infancy. They occur in up to 2.6% of neonates and up to 12% of children by the first year [1,2,3]. A subgroup of patients with IH exhibit associated structural anomalies of the brain, cerebral vasculature, eyes, aorta, and chest wall in the neurocutaneous disorder called PHACES syndrome. IH typically present in 2 phases; a phase of rapid proliferation which occur in the first year of life, followed by a slow gradual involution over the next 5 to 7 or more years. IH remain asymptomatic and can, therefore, be managed by close observation. Indications for immediate management include; IH that might cause significant complications such as amblyopia, airway obstruction, bleeding and ulceration, high output cardiac failure .
A 1 year 8 months old girl with congenital sternal defect was referred from Roan General Hospital to Arthur Davidson Children’s’ Hospital for further management. The patient was born at term via spontaneous vaginal delivery at the university Teaching Hospitals Women and New-born Hospital with no perinatal complications. She presented with a 4/12 history of swelling on left upper eyelid, left side of the face and lower lip which increased in size progressively. The patient being a child, consent to have the case report published was obtained from the mother.
On examination, patient had a stable general condition, Visual acuity (VA) in both eyes was central, steady and maintained, that is, the patient was able to fix and follow moving targets. The intraocular pressure was 11 mmHg and 12 mmHg in the right and left eyes respectively. The right eye had normal anterior and posterior segments. Left eye had a lesion, measuring about 6 by 4 cm, on the upper eyelid which was blanching with pressure. There was mechanical ptosis on the affected eye and smaller other lesions were noted on lower lips also (figs 1 and 2). Systemic examination revealed a sternal cleft deformity with a holosystolic murmur, and supraumbilical raphe. Chest x-ray revealed an enlarged cardiac shadow and a small ventricular septal defect (VSD) was noted on echocardiogram. The ECG and abdominal u/s were normal. The parameters on Full blood count were within normal limits. Unfortunately, MRI or CT scan of the brain and orbit were not done because the patient’s care-givers could not afford to do the investigations due to the cost involved.
A diagnosis of PHACES syndrome was made based on above findings and multi-disciplinary approach was employed in the management of the patient. The teams involved were Ophthalmology, Paediatric Surgery, General Paediatrics, and Cardiology. Monthly doses of intralesional methylprednisolone were administered for 3 months. The outcome was complete resolution of the lesions as shown in fig 3.
Fig 1: Showing the child with a swollen left eye upper eyelid
Fig 2: Showing lesions on the lower lip
Fig 3: Showing a regressed lesion after treatment
PHACES syndrome is a group of disorders characterized by posterior fossa abnormalities, haemangioma, arterial lesions, cardiac abnormalities/coarctation of the aorta [1,2,3]. The first description of PHACE syndrome with brain abnormalities was reported in 1978 by Pascual-Castoviejo  in 1996 while acronym PHACE was created by Frieden et al in 1996; this gave the details of the most representative features of the syndrome . The acronym has been expanded to PHACES which includes supraumbilical raphe and sternal clefting ) .
In 2009, a consensus to define the diagnostic criteria for PHACES syndrome was arrived at. These criteria were divided into 2 categories that is PHACES syndrome or possible PHACES syndrome. Major and minor criteria were determined for the following organ systems: cardiovascular, cerebrovascular, ocular, structural brain, ocular, and ventral/midline.The diagnosis of PHACES Syndrome requires the presence of a characteristic segmental haemangioma greater than 5cm on the face or scalp plus 1 major criterion or 2 minor criteria while possible PHACE requires the presence of a characteristic segmental haemangioma greater than 5cm on the scalp or face plus 1 minor criterion . Our patient presented with a haemangioma affecting the left upper eyelid about 6x 4 cm in size, sternal cleft deformity, umbilical raphe and as small ventricular septal defect. Sternal cleft deformity and umbilical raphe represented the major criteria while ventricular septal defect the minor criteria. Therefore, the presence of above features in our patient satisfied the criteria for diagnosis of PHACES syndrome.
Haemangiomas in PHACES syndrome are more common in female with a female: male ratio of 9:1 ratio for the latter . They are typically bulky, plaque-like lesions involving several cervicofacial segments, but without being confined by their boundaries. They have a segmental distribution which partially corresponds to developmental facial prominences. Facial haemangioma patterns have been described into four segments: frontotemporal (S1), maxillary (S2), mandibular (S3) and frontonasal (S4) segments. The majority of PHACE patients have haemangioma involving the S1 segment regardless of other segment involvement. The facial segmental involvement is also associated with clinical manifestation. Haemangiomas located in the S1 & S4 segments are associated with structural brain, cerebrovascular and ocular anomalies, while those located in the S3 segment are associated with sternal defects or supraumbilical raphes. About 22% of patients present with extracutaneous haemangioma with the most affected ones having only one extracutaneous manifestation to fulfil a diagnosis of PHACE syndrome; the most common ones being CNS anomalies [1,7].
The first description of the association of PHACE syndrome with brain abnormalities was reported in 1978 by Pascual-Castroviejo. He reported that between 43% and 90% of patients with PHACES have a CNS structural malformation. Malformations typically involve the posterior fossa, presenting as a Dandy-Walker complex, isolated cerebellar hemispheric hypoplasia, or a combination of the 2. Dandy–Walker malformation is the most common associated developmental abnormality [1,7].
Vascular anomalies are the most frequent malformation associated with cutaneous haemangioma–vascular complex syndrome. Absence of the internal carotid and/or vertebral arteries and persistence of the trigeminal artery are the most common malformations . Cardiac anomalies include; patent ductus arteriosus, ventricular septal defects, arterial septal defects, pulmonary stenosis, tricuspid aortic valve, arterial enlargement, ventricular hypertrophy, tetralogy of Fallot, and patent foramen ovale. The case we presented had a Ventricular septal defect which was confirmed by echocardiogram .
Approximately one-third of the PHACE(S) syndrome cases have eye involvements . In a recent study on 23 cases of PHACE(S) syndrome, 14% of the cases showed ocular involvement . The reported ocular manifestations of this syndrome could be posterior segment abnormalities which include morning glory disk anomaly, retinal vascular anomalies, optic nerve hypoplasia and atrophy, while anterior segment abnormalities include cataract, microphthalmia, conjunctival haemangioma, posterior embryotoxon, Mittendorf dots, corneal opacity, sclerocornea, iris coloboma, iris heterochromia, iris hypoplasia, and iris vessel hypertrophy. There can also be presence of miscellaneous ocular abnormalities such as congenital glaucoma, cryptophthalmos, proptosis, Horner syndrome, congenital 3rd or 4th nerve palsies, strabismus, and ptosis .
Sternal defects and supraumbilical raphe were encountered in 43 patients with PHACES syndrome. Matry et al. reported three patients with subtle sternal pits without underlying soft-tissue or bony loss in a series of 14 patients with PHACES syndrome. Our patient presented with both sternal defect and supraumbilical defect .
Observation remains the mainstay of treatment of capillary haemangiomas since most lesions regress on their own. However, intervention is indicated in the following circumstances; occlusion of the visual axis, optic nerve compression, severe proptosis, anisometropia, maceration and erosion of the epidermis, infection, and cosmetic disfigurement . Obstruction of the visual axis in our case was the reason why we had to intervene in order to prevent amblyopia. The management option can either be surgical ormedical depending on the size and location of the lesion. Medical management options include; Steroids- topical, intralesional or systemic, interferon alfa-2a therapy, Vincristine, Propranolol therapy or timolol therapy. Our patient responded well after administration of 3 doses of intralesional methyl-prednisolone [1,11].
Intralesional injection of corticosteroids has proven to be effective in the management of cutaneous infantile haemangiomas. In this case we highlighted the successful management of a 1 year 8 months old girl who presented with a haemangioma affecting the left eyelid and causing mechanical ptosis and had other features of PHACES syndrome. The haemangioma was successfully treated with intralesional steroid injections.
- Sami N. Alsuwaidan. PHACES syndrome in association with airway haemangioma: First report from Saudi Arabia and literature review. Ann Thorac Med. 2012 Jan-Mar; 7(1): 44–47
- Pornpun Sripornsawan, Thirachit C, Supika K. Successful Treatment of PHACE Syndrome with Oral Propranolol.
- Reese V, et al. Association of facial haemangiomas with Dandy-Walkerand other posterior fossa malformations. J Pediatr. 1993. [PubMed]
- Anita Rotter, Luciana Paula Samorano, Maria CecíliaRivitti-Machado, Zilda Najjar Prado Oliveira, Bernardo Gontijo. PHACE syndrome: clinical manifestations, diagnostic criteria, and management5
- Nayak L, Nayak B, Sinha G, Khokhar. PHACE syndrome with lip haemangioma, microphthalmos and persistent fetal vasculature. BMJ case Rep March 31 2016[PubMed]
- Metry DW, Heyer G, Hess C, Garzon M, Haggstrom A, Frommelt P, et al. Consensus statement on diagnostic criteria for PHACE syndrome. Pediatrics 2009; 124:1447-56
- V.S. Oza, E. Wang, A. Berenstein, M. Waner, D. Lefton, J. Wells and F. Blei. PHACES Association: A Neuroradiologic Review of 17 Patients. American Journal of Neuroradiology April 2008, 29 (4) 807-813
- Pascual-Castroviejo I. Vascular and nonvascular intracranial malformations associated with external capillary haemangiomas. Neuroradiology. 1978;16:82–4. [PubMed] [Google Scholar]
- Melnick L.E., Yan A.C., Licht D.J., Treat J.R., Castelo-Soccio L. PHACE syndrome: a retrospective review of 23 patients. Pediatr Dermatol. 2014;31:390-392. [PMC free article] [PubMed] [Google Scholar]
- Assari R, et al. PHACE(S) syndrome: Report of a case with new ocular and systemic manifestations. J Curr Ophthalmol. 2016 Dec 27; 29(2): 136-138
- Youssef JS. Quaraishi, HA, Cervicofacial haemangioma and its association with PHACE syndrome, Otolaryngol Head Neck Surg. 2003; 128:758-60. [PubMed]