Juvenile Hemangiomas: New Concepts and Management Strategies

The emergence of multidisciplinary vascular anomalies teams over the past decade has advanced understanding and revolutionized management of vascular lesions. Most common among these lesions is the juvenile hemangioma, known to ophthalmologists as the “capillary hemangioma.” Because juvenile hemangiomas demonstrate a predilection for the ocular adnexa, ophthalmologists are critical to successful management and must remain current in terminology and treatment.

History

Between 1982 and the end of the 20th century, vascular anomalies were classified primarily by endothelial biology and clinical behavior, a useful scheme that distinguished hemangiomas from vascular malformations (Mullikin et al, 1982:412-422). Newly developed immunohistochemical stains can now definitively distinguish hemangiomas from other vascular lesions (North et al, Facial Plast Surg Clin North Am., 2001:505-517). Despite overwhelming acceptance in the medical community at large, modern classification remains illusive in ophthalmology, an unfortunate fact that too often leads to miscommunication, misdiagnosis, and mistreatment.

Biology

Hemangiomas are rapidly evolving, benign neoplasms that proliferate over several weeks or months in the early postnatal period, stabilize, and naturally involute over the ensuing decade. Ninety percent are diagnosed within the first month of life, and a lesion arising after 3 months of life suggests another diagnosis. Hemangiomas arise most commonly in the head and neck, and frequently involve the eyelids and orbit. Cutaneous hemangiomas demonstrate bright red, nodular surfaces; subcutaneous hemangiomas are bluish with smooth overlying skin. These are the lesions known as “capillary hemangiomas” in the ophthalmic literature (Haik et al, 1994:399-426). Growing immunohistochemical evidence has linked hemangiomas with placental endothelia, raising the possibility of placental origin of these lesions (North et al, Arch Dermatol., 2001:559-570).

The completely distinct, so-called “cavernous hemangioma” displays not one of the clinical, light-microscopic, or immunohistochemical characteristics of a true hemangioma: it does not proliferate, it never involutes, and its endothelium displays neither GLUT-1, Lewis Y, nor merosin antigens, markers found only in placenta, brain, and hemangioma endothelia. These lesions are well encapsulated and have no discernable connection to adjacent vasculature; they are probably variants of venous malformations. When true hemangiomas are excised during the involution phase, the histopathology may be indistinguishable from these orbital venous malformations, further demonstrating the limitations of the outdated terminology.

Clinical Observations

Juvenile hemangiomas involving the eyelids and orbit present a series of clinical concerns. They may arise in isolation, with segmental distribution, or as part of a multisystem hemangiomatosis. The identification of 4 or more externally visible hemangiomas should prompt ultrasound or nuclear magnetic resonance imaging to rule out visceral involvement.

In isolated lesions, the immediate concern is prevention of amblyopia. Deprivation amblyopia can be caused by upper or lower eyelid lesions, or by secondary ptosis (mechanical or myogenic). More common is induced astigmatism, which may also produce amblyopia. Astigmatisms induced by hemangiomas usually persist after involution, whereas our recent studies show that early removal of eyelid hemangiomas allows complete resolution of corneal astigmatism.

The time-tested doctrine of watchful waiting has provided enormous experience with the natural history of hemangiomas. While involution is the rule, it is rarely if ever complete; subcutaneous lesions result in fatty subcutaneous masses, while cutaneous hemangiomas produce permanent crepe-paper cutaneous deformities.

Long-term effects of eyelid and orbit hemangiomas include eyelid notching, lagophthalmos, trichiasis, entropion and ectropion, ptosis, amblyopia, globe dystopia, orbital overgrowth, and facial asymmetry.

Treatment

Numerous treatment modalities are now available to hemangioma patients and their families. Superficial hemangiomas respond well to pulsed-dye laser treatment. These treatments are usually dispersed over 6 to 8 monthly sessions. High-potency topical steroids such as clobetasol (Temovate) have been effective for cutaneous hemangiomas that are broad-based or adjacent to steroid-sensitive structures such as nasal cartilage. Imidazoquinoline is a topical immunomodulator currently under investigation for this application.

Compound or subcutaneous hemangiomas have responded well to intralesional corticosteroid injection, now the preferred route of treatment for isolated periocular hemangiomas (Kushner, 1982:496-506). Treatment with systemic corticosteroids requires a 9 to 14 month course of prednisone 1-4 mg/kg/day, and should be reserved for diffuse lesions or those inaccessible to direct treatment in life- or sight-threatening locations. A typical intralesional regimen includes triamcinolone 40 mg/ml and betamethasone 6 mg/ml injected slowly through separate 1-3 cc syringes. The lesion is intentionally not compressed after injecting in order to avoid retrograde intravascular flow. The injections can be repeated at monthly intervals once or twice. Because of the dreaded but rare potential complication of retinal artery occlusion, some authors have used indirect ophthalmoscopy at the time of injection. The mechanism of action of corticosteroids on hemangiomas is not known, but current theory suggests the steroid sensitizes the vascular endothelium to circulating vasoconstrictive agents. Intralesional injections are most effective during the proliferative phase.

In cases of steroid-resistant hemangiomas, alpha-interferon was used in the past as a second-line systemic treatment. Several cases of irreversible spastic diplegia (spastic paralysis of the lower limbs) have been reported, however, and the medication is no longer recommended for this application (Michaud et al, 2004:1231-1236). Vincristine has been used with some success in extreme cases (Fawcett et al, 2004:168-171).

Surgical excision of hemangiomas in the ocular adnexa has become more common with the advent of hemostatic agents and surgical devices. Excision can be more effective in the early involutional phase when the tissue-expanding effects of the mass permit direct closure of even quite significant surgical defects. Referral for oculoplastic reconstruction in the early involutional phase, even in cases beyond the risk of functional ophthalmic complications, can provide the patient the best cosmetic and often psychological outcome. In typical cases of eyelid compound hemangiomas, intralesional steroids followed by postproliferative surgical excision is evolving into a standard treatment protocol.

Recommendations & Observations

		The presence of 4 or more visible hemangiomas should prompt imaging studies with ultrasound or MRI to rule out visceral involvement.
		Astigmatism induced by hemangiomas can be completely reversed with early intervention.
		Involuted hemangiomas almost always leave permanent residua in the form of dermal or subdermal scar tissue.
		Early excision often provides the best long-term cosmetic and psychological outcome.
		Two cases of central retinal artery occlusion (CRAO) have been reported following steroid injections into eyelid hemangiomas. The technique has been modified to decrease the risk of this complication.
		Systemic corticosteroids require prolonged treatment and should be reserved for extreme or inaccessible lesions that threaten life or sight.
		Due to the irreversible neurologic side effects of interferon, Vincristine has replaced alpha interferon for the treatment of severe hemangiomas.

References

Author Disclosure

The author states that he has no significant financial relationship with the manufacturer or provider of any product or service discussed in this article or with the manufacturer or provider of any competing product or service.