Ophthalmology – Hemangioma in Children

Basics

Description

Infantile hemangioma is a benign vascular tumor of infancy that can involve the eyelids, orbit, or surrounding periorbital tissues. It characteristically undergoes a phase of rapid postnatal growth followed by gradual spontaneous involution.

The main ophthalmic concern is not the tumor itself but its ability to interfere with visual development. A periocular hemangioma can obstruct the visual axis, induce astigmatism or anisometropia, produce ptosis, or cause proptosis, all of which can lead to amblyopia.

Epidemiology

Infantile hemangiomas occur in approximately 1–2.6% of newborns. They are among the most common benign vascular tumors of infancy.

Most lesions become apparent during the first few weeks of life and enlarge rapidly during the first several months.

Risk Factors

Important risk factors include female sex, Caucasian race, prematurity, and a positive family history. An association with chorionic villus sampling has also been reported.

Genetics

Most infantile hemangiomas are sporadic and have no clear hereditary basis.

Rare familial forms have been reported with an autosomal dominant pattern with variable expression, including linkage to chromosome 5q31–33.

Genetic counseling may be appropriate in clearly familial cases or when the child has features of a syndromic vascular disorder.

Pathophysiology

During the proliferative phase, hemangiomas show increased endothelial cell growth and high expression of vascular endothelial growth factor (VEGF) and other proangiogenic factors.

As the lesion enters its involutional phase, angiogenic signaling decreases and endothelial cells undergo apoptosis, allowing the vascular tumor to progressively regress.

Etiology

Infantile hemangiomas represent a benign proliferation of blood vessels. They are often described as hamartomatous vascular growths, although modern classification considers infantile hemangioma a true benign vascular tumor with a characteristic growth and involution cycle.

Commonly Associated Conditions

Large or segmental facial hemangiomas may be associated with PHACE syndrome, which includes posterior fossa abnormalities, large facial hemangiomas, arterial anomalies, cardiac abnormalities including coarctation of the aorta, eye abnormalities, and sternal or ventral developmental defects.

Very large vascular tumors associated with thrombocytopenia and consumptive coagulopathy require urgent evaluation. Importantly, classic Kasabach-Merritt phenomenon is generally associated with kaposiform hemangioendothelioma or tufted angioma rather than typical infantile hemangioma.

Other vascular or developmental syndromes that may enter the differential include Maffucci syndrome and Klippel-Trenaunay syndrome.

Diagnosis

History

The characteristic history is of a vascular lesion that appears shortly after birth and undergoes rapid growth during the first several months of life.

A lesion may initially appear as a small red macule or may not be obvious at birth.

Growth is usually most rapid during infancy. Spontaneous involution begins later, often during the second year of life, and may continue for several years.

Parents should be asked about feeding or breathing difficulty, noisy breathing, skin lesions elsewhere on the body, bleeding, bruising, and any change in fixation behavior.

Physical Examination

A complete ocular examination is required.

Superficial lesions are typically bright red, whereas deeper subcutaneous lesions may have a bluish-purple appearance.

Hemangiomas are generally compressible and may blanch with pressure. They may enlarge or become more violaceous during crying, straining, or dependent positioning.

The size and location of the lesion should be documented, preferably with serial photography.

Particular attention should be paid to whether the lesion obstructs the visual axis, induces ptosis, or causes an abnormal head posture.

Visual Development

Cycloplegic refraction is important because periocular hemangiomas can induce significant astigmatism, anisometropia, or myopic shift.

Even a lesion that does not directly cover the pupil can produce amblyopia through corneal distortion.

Fixation preference, ocular alignment, and age-appropriate visual acuity should therefore be monitored closely.

Orbital Involvement

The examination should assess for proptosis, globe displacement, optic nerve compromise, restricted ocular motility, or fullness of the temporal fossa.

An afferent pupillary defect or reduced vision raises concern for optic nerve compression or another serious orbital complication.

Diagnostic Tests and Interpretation

Laboratory Testing

No laboratory testing is necessary for a typical isolated lesion.

A complete blood count with platelet count may be appropriate in a child with a very large vascular tumor, petechiae, bleeding, or concern for a consumptive coagulopathy.

Ultrasound

Ultrasonography can demonstrate a compressible vascular lesion with internal blood flow.

Doppler imaging can help confirm the vascular nature of the mass.

MRI

MRI is preferred when deeper orbital involvement, extensive facial disease, PHACE syndrome, or possible intracranial extension is suspected.

It provides excellent visualization of the lesion’s extent and relationship to the orbit, brain, and vascular structures without ionizing radiation.

CT

CT may demonstrate associated bone changes but is generally avoided when MRI can provide the necessary information because of radiation exposure in infants.

Biopsy

Biopsy is rarely needed when the clinical appearance is typical.

It may be considered when an atypical rapidly growing orbital mass raises concern for rhabdomyosarcoma or another neoplasm.

Pathological Findings

During the proliferative phase, lesions show dense proliferation of small capillary-sized vessels lined by plump endothelial cells, often accompanied by pericytes and other stromal cells.

During involution, endothelial proliferation declines and vascular tissue is progressively replaced by fibrofatty tissue.

Differential Diagnosis

Important differential diagnoses include rhabdomyosarcoma, lymphatic malformation, venous malformation, congenital vascular malformation, port-wine stain, arteriovenous malformation, neuroblastoma metastasis, encephalocele, and dacryocystocele.

A port-wine stain differs from an infantile hemangioma because it is a capillary malformation present at birth that generally grows proportionally with the child rather than undergoing a rapid proliferative phase followed by spontaneous involution.

Treatment

Many periocular hemangiomas can be observed if they do not threaten vision, cause significant disfigurement, ulcerate, or produce other functional complications.

Treatment becomes necessary when there is risk of amblyopia, visual axis obstruction, rapidly progressive orbital disease, significant astigmatism or anisometropia, optic nerve compression, ulceration, or major cosmetic deformity.

Amblyopia Management

Amblyopia should be treated aggressively when present.

Management may include full spectacle correction, patching of the better-seeing eye, or atropine penalization, depending on the child’s age and the degree of visual asymmetry.

Correction of refractive error is essential even when tumor-directed therapy is being used.

Beta-Blocker Therapy

Propranolol is now the standard first-line systemic treatment for most vision-threatening infantile hemangiomas.

It can produce rapid softening, color change, and shrinkage of the lesion.

Treatment is usually coordinated with pediatrics or another clinician experienced in infantile hemangioma therapy because propranolol can cause bradycardia, hypotension, bronchospasm, and hypoglycemia, particularly in young infants.

Dosing and initiation protocols vary according to age, weight, comorbidities, and local practice.

Contraindications or important precautions include significant bronchospastic disease, certain cardiac abnormalities, and some cerebrovascular abnormalities, particularly in patients being evaluated for PHACE syndrome.

Topical Timolol

Topical timolol may be useful for selected small, superficial periocular hemangiomas.

Because systemic absorption can occur, especially in infants, it should still be used with appropriate caution and monitoring.

Deep orbital lesions generally require systemic rather than topical therapy.

Corticosteroids

Systemic corticosteroids were historically the principal treatment before the widespread use of propranolol.

They may still be considered when beta-blockers are contraindicated or ineffective.

Potential complications of prolonged systemic corticosteroid therapy include growth suppression, adrenal suppression, immunosuppression, hypertension, and Cushingoid changes.

Intralesional corticosteroid injection is now used much less often because of serious potential complications, including retinal artery occlusion, skin necrosis, depigmentation, and subcutaneous fat atrophy.

Other Medical Therapies

Interferon alfa is rarely used today because of significant neurologic and systemic toxicity.

Other systemic agents may be considered for unusually aggressive or treatment-resistant vascular tumors under specialist guidance, but these are not routine first-line therapies for typical infantile hemangioma.

Laser Treatment

Laser therapy can be helpful for selected superficial residual or ulcerated lesions, particularly when treatment is directed primarily at surface components.

Pulsed dye laser is generally more relevant than older destructive laser techniques.

Laser therapy is not usually sufficient for a deep orbital hemangioma.

Surgery

Surgery is rarely required during the proliferative phase because many lesions respond well to medical therapy and later involute spontaneously.

Partial or complete excision may be considered for sight-threatening lesions resistant to medical treatment, lesions producing persistent mechanical problems, or residual deformity after involution.

Reconstructive or cosmetic surgery is often best deferred until involution has substantially completed when possible.

Referral

Urgent otolaryngology evaluation is indicated when an airway hemangioma is suspected.

Genetics evaluation is appropriate for suspected PHACE syndrome, familial disease, or other syndromic findings.

Hematology evaluation is required if there is thrombocytopenia or concern for a consumptive coagulopathy.

Neurology, neurosurgery, cardiology, or vascular anomaly specialists may be required when there is intracranial, arterial, cardiac, or extensive orbital involvement.

Inpatient Considerations

Hospitalization may be appropriate for infants with airway compromise, severe systemic disease, or significant cardiorespiratory risk during initiation of systemic beta-blocker therapy.

Whether propranolol is started as an inpatient or outpatient depends on the child’s age, medical status, treatment protocol, and local practice.

Follow-Up

Close ophthalmic follow-up is essential during the proliferative phase.

Monitoring should include visual acuity or fixation behavior, cycloplegic refraction, ocular alignment, lesion size, ptosis, globe position, and optic nerve function.

Rebound growth can occur after discontinuation of beta-blocker or corticosteroid therapy, so follow-up should continue after treatment is stopped.

Once active growth has ceased, follow-up can be adjusted according to residual refractive error, amblyopia, and cosmetic concerns.

Patient Monitoring

The two principal ophthalmic monitoring targets are vision and refraction.

Children with periocular hemangiomas are particularly vulnerable to amblyopia from astigmatism, anisometropia, ptosis, or direct visual-axis obstruction.

Psychosocial effects of a visible facial lesion should also be considered as the child grows.

Patient Education

Parents should understand that many hemangiomas eventually involute spontaneously, but lesions near the eye require closer observation because visual development can be permanently affected.

They should seek prompt medical attention for wheezing, stridor, feeding or breathing difficulty, sudden lesion enlargement, bleeding, petechiae, reduced fixation, or increasing eyelid closure.

Families should also understand that even after the lesion shrinks, refractive error and amblyopia may persist and require continued treatment.

Prognosis

The overall prognosis is very good.

Many infantile hemangiomas undergo substantial spontaneous involution during childhood.

The visual prognosis depends mainly on whether amblyopia is prevented or treated early.

Periocular hemangiomas frequently induce astigmatic or anisometropic refractive errors, and untreated refractive asymmetry can result in permanent reduction of vision.

Complications

Potential complications include amblyopia, induced astigmatism, anisometropia, ptosis, proptosis, optic nerve compression, corneal exposure, residual eyelid deformity, skin atrophy, scarring, hypopigmentation, facial asymmetry, and psychosocial distress.

The most important preventable ophthalmic complication is permanent amblyopia from untreated visual deprivation or refractive error.