AUTHOR AND EDITOR INFORMATION

Section 1 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

INTRODUCTION

Section 2 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Background

Capillary hemangiomas are one of the most common benign orbital tumors of infancy. They are benign endothelial cell neoplasms that are typically absent at birth and characteristically have rapid growth in infancy with spontaneous involution later in life. This is in contrast to another known group of childhood vascular anomalies, vascular malformations. Vascular malformations, such as lymphangiomas and arteriovenous malformations, are present at birth and are characterized by very slow growth with persistence into adult life.

Pathophysiology

Capillary hemangiomas are believed to be hamartomatous proliferations of vascular endothelial cells. They are now thought to be of placental origin due to a unique microvascular phenotype shared by juvenile hemangiomas and human placenta. Periorbital capillary hemangiomas follow a similar course to hemangiomas on other parts of the body. They generally exhibit 2 phases of growth, a proliferative phase and an involutional phase. The proliferative phase of rapid growth typically occurs from 8-18 months. Pathologically, it is characterized by an increased number of endothelial and mast cells, the latter being a stimulus for vessel growth. Endothelial cell proliferation returns to normal following the proliferation phase.

The involutional phase is characterized by slow regression of the hemangiomas. One half of all lesions will involute by age 5 years, and 75% will involute by age 7 years. During this phase, mast cell numbers decrease to normal and there is a decrease in endothelial and mast cell activity. These vascular spaces become lined with endothelial cells without muscular support.

Frequency

United States

As many as 50% of systemic capillary hemangiomas can occur in the head and neck region. Of all the patients that eventually develop capillary hemangiomas, 30% of them have evidence of their presence at birth, while 100% have manifest them by age 6 months.

Mortality/Morbidity

Systemic involvement with hemangiomas can be a significant source of morbidity and mortality.

• The Kasabach-Merritt syndrome is associated with mortality rates from 30-50%. These patients characteristically present with a consumption coagulopathy and thrombocytopenia secondary to platelet sequestration in large visceral hemangiomas. Disseminated intravascular coagulation may occur. These patients also experience high-output congestive heart failure. Nasopharyngeal hemangiomas can be associated with respiratory obstruction. Surgical intervention often is required in these cases.
• The ophthalmic morbidity of hemangiomas is largely related to their space-occupying effects. The most devastating ophthalmic complication of hemangiomas relates to their ability to cause deprivation amblyopia in the affected eye if the lesion is large enough to directly occlude the visual axis. If the lesion is large enough to cause corneal distortion and astigmatism, anisometropic amblyopia will result.

Sex

Females outnumber male patients with hemangiomas by a ratio of 3:1.

Age

Capillary hemangiomas are present in approximately 1-2% of neonates. All patients that eventually develop hemangiomas have them by age 6 months.

CLINICAL

Section 3 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

History

• The history can be quite variable in this group of patients. Typically, parents may notice a red spot growing in size and thickness in the periorbital area.
• The parents may be acutely aware of a gradual inability of the child to use the vision in the affected eye.

Physical

• Patients usually present with a unilateral, superonasal, eyelid, or brow lesion. It typically blanches with pressure, unlike the lesions seen with port-wine stains. The mass lesion may be sufficient to cause a ptosis of the involved eyelid. Alternatively, if the lesion extends posteriorly in the orbit, proptosis and visual loss may be present.
• Examination of the visual system may reveal decreased visual acuity on the ipsilateral side.
• Unfortunately, amblyopia is seen in 43-60% of patients with eyelid hemangiomas.
• Anisometropia also can be found on examination as a result of the mass effect on the cornea. The axis of plus cylinder is usually toward the hemangioma.

Causes

Capillary hemangiomas are believed to be hamartomatous proliferations of vascular endothelial cells.

DIFFERENTIALS

Section 4 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Other Problems to be Considered

Rhabdomyosarcoma
Lymphangioma
Neuroblastoma
Arterial venous malformations

WORKUP

Section 5 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Lab Studies

• Immunohistochemical staining is positive for factor VIII.

Imaging Studies

• Ultrasonography shows a lesion with irregular contour and low-to-medium internal reflectivity.
• Neuroimaging can be of great assistance in making the diagnosis.
• CT scan reveals a poorly circumscribed mass with no bony erosion. The lesion usually enhances with intravenous contrast.
• Magnetic resonance imaging reveals a lesion that is hypointense to fat on T1-weighted scans and hyperintense to fat on T2-weighted scans.
• A well-circumscribed lobular pattern with prolonged parenchymal staining is seen with angiography. Involuting lesions tend to have less tissue staining.

Histologic Findings

Pathological findings include proliferation of a single layer of endothelial cells and pericytes. Endothelial cells of the basement membrane characteristically have large amounts of endoplasmic reticulum. The small vascular spaces lead to the formation of a high-flow lesion.

TREATMENT

Section 6 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical Care

The indications for treatment can be divided into systemic, ophthalmic, and dermatologic reasons. Systemic reasons for intervention include congestive heart failure, thrombocytopenia, hemolytic anemia, and nasopharyngeal obstruction. Ophthalmic indications for intervention include occlusion of the visual axis, optic nerve compression, severe proptosis, and anisometropia. Dermatologic indications for intervention include maceration and erosion of the epidermis, infection, and cosmetic disfigurement.

• The first-line treatment for capillary hemangiomas is simple observation. Since most of these lesions regress on their own, there is no need to intervene unless one of the above criteria is met.
• Corticosteroids, in various formulations, also have been used in the treatment of capillary hemangiomas.
  • Topical steroid formulations, such as clobetasol propionate cream, can be applied topically to the lesion. The response to these treatments, even with the strongest corticosteroid formulations, is slower than other methods because several weeks are required to obtain a response.
  • Complications include dermal atrophy, pigmentary changes in the skin, and dermatitis, as well as less common ophthalmic complications such as elevated intraocular pressure and cataract formation. Systemic absorption also can occur.
  • Overall, this modality is not appropriate for vision-threatening lesions.
• Injectable steroid formulations also are used in the treatment of these lesions.
  • Endothelial cell sensitization to catecholamines is the mechanism by which intralesional corticosteroids exert their effects. Although there may be a period of temporary enlargement, blanching usually is noted within 2-3 days and involution is seen by 2-4 weeks. Their effectiveness is most pronounced 2 weeks after injection but can be seen up to 2 months later. The overall success rate for this intervention is 75%.
  • The injection is not given directly into the lesion (because it could produce tissue sloughing) but deep into the surrounding tissues with more room for injection. Risks of injection exist even with this maneuver, including lid necrosis, depigmentation, and fat necrosis. The most disconcerting adverse effect concerns reports of central retinal artery occlusion following the intralesional injection of corticosteroids. Although the precise pathogenesis is uncertain, some suggest it may be related to anomalous vessels. A technically slower injection of corticosteroid or a smaller volume of solution may lessen the risk.
  • Steroid injections can be repeated, but, ideally, they should be separated in time by 2-3 months to allow for adrenal recovery. Adrenal suppression after cutaneous steroid injections has been reported.
• Systemic corticosteroids are used for amblyogenic life-threatening lesions.
  • An excellent response rate can be expected in 30% of patients, a questionable response in 40%, and no response in 30% when systemic corticosteroids are used under close observation. The response may be quite dramatic within the first 2 weeks, and the effect may last from 1-4 months. Doses of 2-3 mg/kg may be necessary for up to several months.
  • Complications of systemic therapy with corticosteroids include Cushingoid changes, personality changes, gastrointestinal irritation, oral candidiasis, delayed growth, diabetes, hypertension, and rebound growth of hemangiomas on cessation.
• Interferon alfa-2a has emerged as a new modality to combat the life-threatening and vision-threatening hemangiomas of infancy that are resistant to steroid treatment. While it has potent effects on these lesions, it is commonly associated with adverse effects of varying severity.
• • Interferon alfa-2a exerts its effect by preventing endothelial cell migration in capillary hemangiomas. Authors have shown significant tumor regression after treatment with interferon.
  • Unfortunately, adverse effects from treatment may have somewhat dampened the initial excitement with this treatment. Adverse effects include fever, chills, arthralgias, and retinal vasculopathy. Of more significance, the incidence of spastic diplegia has been as high as 20% in some reports, leading some to reevaluate the benefits of its use. The long-term effects of interferon on the developing brain are unknown.

Surgical Care

• Laser surgery has been attempted to ameliorate capillary hemangiomas but still is controversial. The hemostatic effects of the carbon dioxide laser have been used with success to surgically remove these lesions. Other lasers used include the argon laser and Nd:YAG laser. The pulsed dye laser is only effective for very superficial lesions; its mechanism of action is too slow for sight-threatening hemangiomas. Overall, variable results have been seen with various laser modalities, and the risks of scarring and ulceration often deter its usage.
• Incisional surgical techniques also have had variable success. Surgical ligation of the hemangiomas produces equivocal results. Vascular embolization of the lesions should be used for large extraorbital hemangiomas only. Primary excision also has been advocated for infantile hemangiomas. Early surgical intervention can be considered as a primary treatment option in selected, isolated capillary hemangiomas without a significant cutaneous component. Surgery can provide definitive early treatment and prevent astigmatism and occlusion-related amblyopia.

Consultations

• Consultations with a pediatrician may be necessary to monitor for the systemic adverse effects if prednisone is used or if there is suspicion of systemic involvement.
• Pediatric dermatologists may have particular expertise in the various treatment options available.

MEDICATION

Section 7 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

The goals of pharmacotherapy are to reduce morbidity and to prevent complications.

Drug Category: Corticosteroids

Have anti-inflammatory properties and cause profound and varied metabolic effects. Corticosteroids modify the body's immune response to diverse stimuli.

FOLLOW-UP

Section 8 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Further Inpatient Care

• Young patients may require inpatient admission and monitoring if high doses of systemic steroids are administered.

Further Outpatient Care

• Concerns must be reiterated about ensuring that children with potentially amblyogenic capillary hemangiomas obtain frequent assessments of their visual acuity and refraction. Treatment would be indicated if astigmatism is greater than 1.5-2 diopters or if there is occlusion of the visual axis.

In/Out Patient Meds

• Patients started on systemic steroids may need to be monitored continually on an outpatient basis until either an adequate response is seen or complications preclude its continuation.

Prognosis

• The prognosis for cosmetic and visual recovery is excellent if treatment is instituted at an appropriate time and careful attention is paid to the visual development. Most lesions involute by age 5 years.

MISCELLANEOUS

Section 9 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical/Legal Pitfalls

• The primary concern with capillary hemangiomas is related to their ability to cause permanent, dense amblyopia with the potential for an irrecoverable loss of vision. Close collaboration with ophthalmologists is essential to ensure that sudden changes in vision are promptly detected and treated.
• Vision loss after intralesional corticosteroid injection is a concern of all specialists managing this problem. Parents should be informed of this risk but also cautioned against withholding treatment on the basis of this rare event.

REFERENCES

Section 10 of 10

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

• Assaf A, Nasr A, Johnson T. Corticosteroids in the management of adnexal hemangiomas in infancy and childhood. Ann Ophthalmol. Jan 1992;24(1):12-8. [Medline].
• Barlow CF, Priebe CJ, Mulliken JB, et al. Spastic diplegia as a complication of interferon Alfa-2a treatment of hemangiomas of infancy. J Pediatr. Mar 1998;132(3 Pt 1):527-30. [Medline].
• Boon LM, MacDonald DM, Mulliken JB. Complications of systemic corticosteroid therapy for problematic hemangioma. Plast Reconstr Surg. Nov 1999;104(6):1616-23. [Medline].
• Cruz OA, Zarnegar SR, Myers SE. Treatment of periocular capillary hemangioma with topical clobetasol propionate. Ophthalmology. Dec 1995;102(12):2012-5. [Medline].
• Deans RM, Harris GJ, Kivlin JD. Surgical dissection of capillary hemangiomas. An alternative to intralesional corticosteroids. Arch Ophthalmol. Dec 1992;110(12):1743-7. [Medline].
• Elsas FJ, Lewis AR. Topical treatment of periocular capillary hemangioma. J Pediatr Ophthalmol Strabismus. May-Jun 1994;31(3):153-6. [Medline].
• Haik BG, Karcioglu ZA, Gordon RA, Pechous BP. Capillary hemangioma (infantile periocular hemangioma). Surv Ophthalmol. Mar-Apr 1994;38(5):399-426. [Medline].
• Kavanagh EC, Heran MK, Peleg A, Rootman J. Imaging of the natural history of an orbital capillary hemangioma. Orbit. Mar 2006;25(1):69-72. [Medline].
• Kushner BJ. Intralesional corticosteroid injection for infantile adnexal hemangioma. Am J Ophthalmol. Apr 1982;93(4):496-506. [Medline].
• O'Keefe M, Lanigan B, Byrne SA. Capillary haemangioma of the eyelids and orbit: a clinical review of the safety and efficacy of intralesional steroid. Acta Ophthalmol Scand. Jun 2003;81(3):294-8. [Medline].
• Rosca TI, Pop MI, Curca M, et al. Vascular tumors in the orbit--capillary and cavernous hemangiomas. Ann Diagn Pathol. Feb 2006;10(1):13-19. [Medline].
• Shorr N, Seiff SR. Central retinal artery occlusion associated with periocular corticosteroid injection for juvenile hemangioma. Ophthalmic Surg. Apr 1986;17(4):229-31. [Medline].
• Slaughter K, Sullivan T, Boulton J, et al. Early surgical intervention as definitive treatment for ocular adnexal capillary haemangioma. Clin Experiment Ophthalmol. Oct 2003;31(5):418-23. [Medline].
• Weiss AH. Adrenal suppression after corticosteroid injection of periocular hemangiomas. Am J Ophthalmol. May 15 1989;107(5):518-22. [Medline].

Article Last Updated: Jun 18, 2006