Capillary Hemangioma

From EyeWiki

Capillary hemangioma is one of the most common benign orbital tumors of childhood. In cutaneous hemagniomas, it presents as a red, raised lesion, while subcutaneous lesions can be dark blue and may extend into the orbit. Capillary hemangiomas have a predilection for the upper eyelid and can induce astigmatic anisometropic and/or occlusion amblyopia. Although the diagnosis is made clinically, it is helpful to obtain imaging to delineate the extent of orbital involvement. The natural course of the capillary hemangioma is initial enlargement followed by spontaneous regression. Therefore, treatment is only initiated for lesions threatening vision (from amblyopia, exposure keratopathy, optic neuropathy). The current first-line treatment is beta-blockers, systemically and topically. Other choices of therapy include corticosteroids, both oral and injected, surgical excision, and possibly embolization. It is also important to look for other systemic associations of capillary hemangiomas.


Disease Entity

Demographics:

Capillary hemangioma is the most common benign periorbital tumor of childhood. It is present in 1-2% of all births. There is a 3:1 ratio of females to males. The incidence of orbit and eyelid hemangiomas is 1/10 that of systemic hemangiomas, which occurs in 10% of all children by 1 year of age (1).


Anatomical locations:

A capillary hemangiomas is classified according to its location. It is most commonly found on the eyelid or brow, with a predilection for the upper eyelid. The involvement can be cutaneous, subcutaneous, or with orbital extension.


Pathology:

Capillary hemangiomas are classified as harmartomas, or abnormal proliferation of normal tissue in a normal location, namely endothelial cells. Histologically, the appearance of these lesions depends on the stage of the evolution. Early lesions may be very cellular, with solid nests of plump endothelial cells and little vascular lumen. Established lesions comprise of well-developed, flattened, endothelium-lined capillary channels of varying sizes in a lobular configuration. Involuting lesions show increased fibrosis and hyalinization of capillary walls with luminal occlusion (2).


Diagnosis

Signs and symptoms:

Presentation of capillary hemangiomas usually occurs after birth, but within the first 6 months of life (30% present at birth, 50% by 1-2 months, >90% by 6 months). Clinically, the hemangioma may present as a cutaneous, subcutaneous, or orbital lesion. In cutaneous lesions, the mass is raised, nodular, and bright red. A subcutaneous lesion may appear dark blue or purple. A lesion extending into the orbit may cause proptosis without overlying skin findings. Often, a capillary hemangioma may enlarge and/or change color with crying; and a cutaneous lesion may blanch with pressure and may have a spongy consistency on palpation. However, capillary hemangiomas are without pulsation and have no bruit (3).

Upper eyelid capillary hemangiomas can cause mechanical ptosis. This can lead to reduced visual acuity due to amblyopia from induced astigmatic anisometropia, strabismus, or occlusion by the eyelid itself. Astigmatic anisometropic amblyopia is the most common cause of visual impairment and results from direct pressure on the cornea by the thickened eyelid. Deprivational amblyopia occurs when the growing capillary hemangioma occludes the visual axis. Strabismus can occur if the orbital hemangioma exerts mass effect on the globe causing displacement or involves the extraocular muscles.


Imaging:

Although the diagnosis is clinical in cutaneous lesions, ultrasound should be used to image the extent of periorbital involvement. If deeper orbital extension is suspected, then CT or MRI may be used. On ultrasound, a capillary hemangioma shows high internal reflectivity with irregular acoustic structures. On CT, the lesion shows a low flow prominence with no disturbance of surrounding tissue and no bony erosion; it enhances with contrast. On MRI, the lesion appears hypointense on T1 and hyperintense on T2; it also enhances with gadolinium.


Differential Diagnosis:

- nevus flammeus (port-wine stain) of Sturge-Weber syndrome

- lymphangioma or other vascular malformations

- metastatic neuroblastoma


Management

The course of capillary hemangiomas is characterized by initial enlargement followed by spontaneous regression. 40% of lesions completely involute by age 4, and 80% by age 8 (4). Hence, the management of capillary hemangiomas depends on the location and whether the lesion causes visual impairments. Indications for treatment include amblyopia, optic nerve compression, exposure keratopathy, severe cosmetic defect, infection or necrosis.


Medical:

In the past, the first line therapy of capillary hemangiomas was corticosteroids. Systemic, intralesional injection, and topical steroids have been used with varying degrees of success. Systemic therapy showed some benefit in diffuse or orbital lesions (5). But rebound growth after discontinuation, and significant side effects such as increased risk for growth delay, immunosuppression, behavioral disturbances, adrenal insufficiency made the therapy suboptimal. Intralesional steroid injection was the preferred first-line treatment. It has proven efficacious in diminishing the size of the lesion rapidly within two weeks of injection in many cases (6). However, intralesional steroid injections carry significant risks and complications, including CRAO from embolization of the steroid material, skin necrosis, skin hypopigmentation and fat atrophy. Topical steroid application has also been suggested. Although with fewer side effects, its efficacy was limited and was recommended only as adjunctive therapy for superficial lesions.

Immunomodulators such as cyclcophosphamide and interferon alpha-2a have also been tried systemically. However, the treatment course takes several months, leading to significant adverse effects such as bone marrow suppression and hepatotoxicity (7).

Beta-blockers, applied topically or used systemically, constitute a new and promising treatment modality. In several recent studies, oral Propranolol has shown remarkable regression in patients with eyelid capillary hemangiomas with induced amblyopia, up to as old as 5 years of age (8, 9, 10). Topical beta-blockers have also been shown to be effective for cutaneous capillary hemangiomas (11). The mechanism of action is multivariate and includes vasoconstriction, decreased expression of bFGF and VEGF which are present during the growth phase of the capillary hemangioma (12), as well as the triggering of apoptosis (13). The side effects of beta-blocker therapy include shortness of breath and bradycardia, hence oral propranolol therapy is contraindicated in patients with asthma. The paradigm of medical therapy for capillary hemangioma is changing with the promising results of the beta-blockers. Several randomized control trials are currently underway.


Surgical:

Laser photocoagulation with pulsed-dye laser has been used to stimulate regression of cutaneous hemangiomas. It is currently recommended as adjunctive therapy for very superficial lesions.

Surgical excision remains an option. However, complete excision is difficult as the hemangiomas tend to be unencapsulated. The potential for hemorrhage is also high, therefore surgical excision is reserved for lesions that are refractory to medical or other forms of therapy yet are still causing vision loss.

Recently, embolization by interventional radiology has reported good outcomes as an alternative to resection.

In addition to treating the hemangioma, it is important to manage the patient’s visual rehabilitation with optimal refraction and occlusive therapy concurrently.


Associations:

In a child with a capillary hemangioma, it may be necessary to look for associated syndromes, such as PHACES (Posterior fossa malformations, Hemangiomas, Arterial anomalies, Coarctation of the aorta, Eye abnormalities, Sternal clefting and supraumbilical raphe), especially if the hemangioma involves more than one dermatome. Maffucci syndrome is another one where the patient has multiple cutaneous and visceral hemangiomas. Kasabach-Merritt syndrome is a consumptive thrombocytopenic coagulopathy where platelets are rapidly sequestered within the vascular lesion. Although rare, this is a condition with high mortality which requires prompt management by multiple subspecialists (14).


References

1. Frieden, I. J. et al. Pediatr Dermatol 2005;22:383–406.

2. “Ophthalmic Pathology and Intraocular Tumors.” Basic and Clinical Science Course. American Academy of Ophthalmology. 2010-2011.

3. “Pediatric Ophthalmology and Strabismus.” Basic and Clinical Science Course. American Academy of Ophthalmology. 2010-2011.

4. Drolet, B.A. et al. “Hemangiomas in Children.” N Eng J Med 1999;341:173-181.

5. Schwartz, S. et al. J AAPOS 2007;11:577–583.

6. Coats, D. K. et al. “SubTenon’s infusion of steroids for treatment of orbital hemangiomas.” Ophthalmology 2003;110:1255–1259.

7. Wilson, M.W. et al. “Low-dose cyclophosphamide and interferon alfa 2a for the treatment of capillary hemangioma of the orbit.” Ophthalmology 2007;114:1007–1011.

8. Vassallo, P. et al. “Treatment of Infantile Capillary Hemangioma of the Eyelid with Systemic Propranolol.” Am J Ophth. 2012 Sep 8.

9. Thooumazet F. et al. “Efficacy of Systemic Propranolol for Severe Infantile Haemangioma of the Orbit and Eyelid: A Case Study of Eight Patients.” Br J Ophth. 2012;96(3):370-4.

10. Missoi, T.G. et al. “Oral Propranolol for Treatment of Periocular Infantile Hemangiomas.” Arch Ophth. 2001;129(7):899-903.

11. Chambers, C.B. et al. “A Controlled Study of Topical 0.25% Timolol Maleate Gel for the Treatment of Cutaneous Infantile Capillary Hemangiomas.” Ophth Plast Recon Surg. 2012;28(2):103-6.

12. D’Angelo, G. et al. “cAMP-dependent protein kinase inhibits the mitogenic action of vascular endothelial growth factor and fibroblast growth factor in capillary endothelial cells by blocking Raf activation.” J Cell Biochem 1997;67:353-66.

13. Sommers Smith, S.K. et al. “Beta blockade induces apoptosis in cultured capillary endothelial cells.” In Vitro Cell Dev Biol Anim 2002;38:298-304.

14. Hall, G. "Kasabach–Merritt syndrome: pathogenesis and management". Br J Haematol 2001;112(4):851–62.

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