Capillary hemangioma of infancy are the most common benign orbital neoplasms in children. Historically, they have been referred to by many names such as infantile hemangiomas, juvenile hemangiomas, hemangioblastomas or strawberry nevi. Currently, the universal vocabulary of capillary hemangioma is followed.[rx]
Capillary hemangiomas and pyogenic granulomas are benign vascular neoplasms that are usually identified clinically by their characteristic features. Capillary hemangiomas most commonly develop in infancy on the head and neck and nearly all spontaneously ingress by the teenage years. Pyogenic granulomas, however, typically present in adults and can be induced by trauma. It is exceedingly rare for capillary hemangiomas to present in adulthood or after trauma. We present an extremely unusual case of capillary hemangioma on the tip of the finger of an adult male presenting immediately after a burn. The mass was clinically diagnosed as pyogenic granuloma but histopathologically diagnosed as a capillary hemangioma. To our knowledge, this is the only presentation of its kind.
A capillary hemangioma (also known as an Infantile hemangioma,[rx] Strawberry hemangioma,[rx]and Strawberry nevus[rx]) is the most common variant of hemangioma which appears as a raised, red, lumpy area of flesh anywhere on the body, though 83% occur on the head or neck area.[rx] These marks occur in about 10% of all births,[rx] and usually appear between one and four weeks after birth.[rx] It may grow rapidly, before stopping and slowly fading. Some are gone by the age of 2, about 60% by 5 years, and 90–95% by 9 years.[rx] Capillary hemangioma is a vascular anomaly.
Capillary hemangiomas of the orbit, also known as strawberry hemangiomas, on account of its coloring, or orbital infantile hemangiomas, are the most common orbital tumors of infancy, and unlike orbital cavernous hemangiomas, they are neoplasms rather than vascular malformations.
Capillary hemangiomas occur 5 times more often in female infants than in males, and mostly in Caucasian populations.[rx][rx] Additionally, low birth weight infants have a 26% chance of developing a hemangioma.[rx][rx]
Types of Capillary Hemangioma
Hemangiomas are usually classified into capillary, cavernous, and mixed hemangioma.
| Capillary hemangioma | Cavernous hemangioma | ||
| Numerous proliferating small thin-walled blood-filled vessels | Deep irregular, dermal tangles of large thin-walled vessels or sinusoids | ||
| Surrounded by a discontinuous layer of pericytes and reticular fibers | Surrounded by a discontinuous layer of endothelial cells | ||
| Single-layer of fattened or plump endothelial cells | Separated by scanty connective tissue |
Hemangiomas classified into capillary, cavernous, and capillary cavernous based on their depth in the dermis and subcutaneous fat [rx]. Ulceration, bleeding, scarring and infection are complications of hemangiomas as well as dysfunction in vision, respiration, hearing, or feeding [rx]. Various therapeutic options for treatment of hemangiomas include observation for spontaneous remission, and using topical, intralesional, and systemic corticosteroids, cryosurgery, interferon, radiation, embolization, and laser therapy as [CO2 laser PDL, KTP and ND-YAG [rx]. We describe a child who was treated successfully for hemangiomas with prednisolone, propranolol and interferon-alpha-2b (INF-α-2b).
Presenting features depend on the location of the lesion. Hemangiomas are classified into the following types: [rx]
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Superficial type
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Deep type
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Mixed type
Clinical features
- Superficial lesions – They appear as bright red, nodular masses typically involving the eyelids. Lesions below the dermis tend to have a deep blue to a purple hue. These lesions can present as skin discoloration, a cosmetic blemish, or an eyelid mass. Capillary hemangiomas may cause mechanical ptosis obscuring the visual axis and producing astigmatism and amblyopia.
- Deep lesions – Deep orbital lesions are invisible to the naked eye. They present with gradually progressive proptosis, strabismus, or decreased visual acuity due to optic nerve compression.
- Mixed lesions – Consist of both superficial and deep components. A characteristic clinical feature of capillary hemangiomas is an increase in size or change in color to dark blue when the child cries or strains which are often noted by the parents. This is due to the increased accumulation of deoxygenated blood. This situation, however, is not pathognomonic of capillary hemangiomas and can present in other vascular anomalies.
- Systemic associations – Cutaneous hemangiomas are sometimes associated with visceral lesions. The presence of four or more superficial lesions should raise suspicion of visceral hemangiomas. The most common site of visceral involvement in the liver.
- Kasabach – Merritt syndrome – Large hemangiomas can result in entrapment and consumption of platelets and other clotting factors resulting in life-threatening hemorrhagic thrombocytopenia. [rx]
- PHASES syndrome – First described in 1996, children presenting with large hemangiomas of the face, neck, and scalp can have associated defects involving the brain, blood vessels, eyes, heart, and chest. It is seen more commonly in females. The syndrome name is an acronym of the different anomalies it compromises. (PHASES – Posterior fossa anomalies, Hemangiomas, Arterial anomalies, Cardiac anomalies, and Eye anomalies)[rx]
Pathophysiology
The natural course of capillary hemangiomas was described as early as 1900. These tumors are generally not present at birth but first, appear within the first few weeks after birth. They appear as small flat plaques of telangiectatic vessels. They undergo rapid proliferation (proliferative phase) between 3-12 months of age. During this phase, the endothelial cells undergo rapid proliferation causing new vessel growth, and the lesions become nodular with a scarlet-colored hue: thus the name ‘strawberry nevus.’ This phase is followed by spontaneous involution of the lesions (involutional phase) usually from about three years of age. Endothelial proliferation comes to a halt, and the lesions are replaced by fibrous tissue. [rx]
Causes of Capillary Hemangioma
Hereditary factors have not been shown to play any role in the development of these neoplasms, but several reports have found them to be uncommon in African races. Factors such as prematurity and low birth weight are associated with a higher risk of developing these neoplasms after birth.[rx]
Symptoms of Capillary Hemangioma
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, and 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 [rx].
Upper eyelid capillary hemangiomas can cause mechanical ptosis. This can lead to reduced visual acuity due to amblyopia from induced astigmatic anisometropia, strabismus, or rarely 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. Deprivation 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.
Diagnosis of Capillary Hemangioma
Histopathology
During the proliferative phase, the tumor consists of anastomosing vascular channels lined by plump endothelial cells and pericytes. As the lesion progresses to the involutional stage, the plump endothelial cells become flattened, and there is increased deposition of fibrous tissue between the vascular channels. [rx]
History and Physical
The primary goal of a thorough history and physical is 2-fold in the setting of symptomatic hemangioma. A clinician must rule out more concerning etiologies and assessment of the patient’s health status in the setting of a planned intervention.
Imaging features
- Ultrasound – Capillary hemangiomas appear as irregular lesions in the orbit demonstrating high internal reflectivity with irregular acoustic structures. A scan shows low to medium reflectivity with high spikes produced by the septae. Increased flow within a lesion can be demonstrated by Doppler echography.[rx]
- Computed Tomography (CT) scan – Capillary hemangiomas appear as well-defined to irregular pre-septal or post-septal, intraconal or extraconal-heterogenous soft tissue masses which enhance with contrast. There is no evidence of calcification or bony erosion. They may appear well-defined or ill-defined.
- Magnetic resonance imaging (MRI) – they appear as well-defined or ill-defined lesions which are hypointense on T1 weighted images and hyperintense on T2 weighted images. The characteristic feature is the presence of flow voids within the lesion. They demonstrate diffuse enhancement with Gadolinium contrast which is best appreciated in fat-suppressed images.
- Plain radiography – Plain radiography is not particularly helpful in the diagnosis of capillary hemangiomas. These tumors are not easily seen or clearly identified on plain film. Soft tissue enlargement can be seen, but bony structures will not show evidence of bony erosion. If there is the rapid growth of the orbital tumor during development, orbital enlargement can be seen. However, none of these findings are diagnostic for capillary hemangioma.
- Angiography – Angiography is rarely used as a diagnostic tool for capillary hemangiomas, as both venography and arteriography are technically difficult, and not without complications. Arteriography is rarely used diagnostically but may be useful in rare situations to identify feeder vessels for possible ligation or embolization in life-threatening hemangiomas that are non-responsive to less invasive therapies.[rx] Feeder vessels may be identified as an enlarged ophthalmic artery, internal maxillary artery, or frontal branch of the superior temporal artery. The tumor often drains into the cavernous sinus via the superior ophthalmic vein.
- Tissue biopsy – Although capillary hemangiomas can often be diagnosed with less invasive techniques, tissue biopsy may be occasionally required, especially in the case of proptosis without superficial involvement. In these cases, the differential diagnosis may include other tumors in this age group, such as lymphangioma, metastatic neuroblastoma, or rhabdomyosarcoma. As all surgeries carry inherent risks of infection, hemorrhage, diplopia, or visual loss, biopsy diagnosis is reserved for cases that cannot be diagnosed with less invasive techniques.
Treatment of Capillary Hemangioma
Capillary hemangiomas are most often asymptomatic thus require no intervention. Around 10% of hemangiomas can present with astigmatism, visually obscuring ptosis, amblyopia, ulceration or bleeding, significant proptosis causing optic nerve compression or exposure keratopathy: these cases which require management. [rx]
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Beta-Blockers – Topical or systemic beta; blockers are currently the mainstay of management for capillary hemangiomas. Following their accidental discovery by Leaute – Labreze and colleagues in 2008 who noticed a regression in cutaneous hemangiomas in children treated with beta; blockers for cardiac and renal problems, propranolol has replaced oral steroids as the treatment modality of choice. [rx] beta; blockers suppress vascular endothelial growth factors (VEGF) and fibroblast growth factors (FGF) which are responsible for proliferation. They also cause down-regulation of cyclic – AMP needed for cell signaling and induce apoptosis of proliferating cells. [rx]
- Oral Propranolol – It is started as a low dosage of 0.16 mg/kg and gradually increased in the absence of complications to 2 mg/kg/day in three divided doses. [rx]
- Topical Timolol – It is useful for superficial lesions and applied as 0.5% gel preparation twice daily until the lesions regress. Reduction in size and change in color can be noticed as early as 1-week after commencing treatment. Treatment should continue throughout the proliferative phase (up to 12 months of age) and gradually tapered and stopped to avoid a rebound increase in size.
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Corticosteroids – Before the advent of beta; blockers, corticosteroids were administered orally or intralesionally. This was the treatment of choice for capillary hemangiomas. [rx] Steroids are effective only during the early proliferative phase and are associated with significant side effects. Complications such as weight gain, cushingoid features, adrenal suppression, hypertension, localized hypopigmentation of skin, fat atrophy and central retinal artery occlusion have been reported thus making this modality a less preferred choice. Steroid injections into lesions that are being removed surgically are still used.
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Immunomodulators. [rx]Agents such as interferon – α, vincristine, cyclophosphamide have been tried in steroid-resistant cases. However, these agents are associated with complications such as bone marrow suppression and hepatotoxicity.
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Lasers – [rx] Superficial hemangiomas can be treated with pulsed–dye lasers which diminish the size and lighten the color of the lesions.
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Radiotherapy – Radiation therapy can be effective in the management of certain capillary hemangiomas. Microembolisms can be created in the tumors by low-level radiation, which can speed the regression of the mass. The involutional response usually occurs in 1-2 weeks, and treatment may be repeated for further resolution. Cumulative doses must be monitored as historically, large doses of radiation with poor delivery or shielding could cause radiation-induced complications of the skin, eyelids, eye, and orbit. Current radiologic technology makes direct radiologic damage rare, however radiation-induced cataracts can still occur with 200-600 rads if the anterior segment is not adequately shielded.[rx]
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Laser Therapy – Carbon dioxide, argon, neodymium-YAG, and flash-lamp pumped-dye laser have all been utilized in the treatment of capillary hemangiomas.[rx,rx] Laser treatments have been found to be more effective for early and superficial lesions and less effective in deeper orbital lesions.[rx,rx,rx] Some physicians have found more success with combination therapy, such as intralesional steroids in combination with laser therapy. There is not yet a defined laser-delivery system or method specific for the different types of hemangiomas and most physicians find results are user-dependent.
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Intralesional corticosteroid injection – Due to the systemic risks of long-term oral steroid use, intralesional corticosteroid injection is more commonly used. A recent study of the American Association for Pediatric Ophthalmology and Strabismus members reported that intralesional steroid injection is the most common treatment and also the most frequent initial therapy.[rx] This modality allows for a high dose of medication directly into the tumor, minimizing systemic absorption. One or two additional injections are usually required after the initial injection. Intralesional corticosteroid injection was first described in nonorbital cutaneous hemangiomas and was reported for periocular lesions by Kushner in 1979. His case series reported success in 3 out of 4 patients with the use of triamcinolone and betamethasone.[rx] Injection can be used most easily with anterior lesions or after biopsy or partial excision of deeper orbital tumors. There have also been descriptions of techniques involving sub-Tenons injection along with the injection of the hemangioma, with satisfactory results.[rx]
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Interferon α – Recombinant interferon alfa, and angiogenesis inhibiting agent, has been used successfully as a secondary agent for life-threatening hemangiomas that have failed corticosteroid therapy.[rx,rx] Both interferon alfa-2a and 2b have been used as subcutaneous injections. The dosing is usually 3 million units per square meter of body-surface area per day. Response to treatment usually ranges from a few weeks to several months. Some of the few common side effects include irritability, liver enzyme abnormalities and neutropenia. The most worrisome side effect is spastic diplegia, which has been reported in up to 20 percent of patients. The mechanism is not understood and is potentially irreversible.
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Vincristine – Due to the serious side effect of spastic diplegia, vincristine replaced Interferon α as the second-line treatment for large capillary hemangiomas resistant to corticosteroids. Vincristine is a microtubule inhibitor, and is also an immunosuppressant used in treating thrombotic thrombocytopenic purpura or chronic idiopathic thrombocytopenic purpura. It has be shown to be efficacious in the treatment of Kasabach-Merritt syndrome with non-orbital capillary hemangiomas.[rx] Side effects include irritability, loss of deep tendon reflexes, and abdominal pain. Intravenously infused vincristine necessitates the use of a permanent venous port in the patient, hence its use is reserved for capillary hemangiomas that are life-threatening and unresponsive to other medications.
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Cyclophosphamide – The use of an alkylating agent for the treatment of capillary hemangioma was first reported by Rush in 1966, with subsequent case reports verifying the efficacy of cyclophosphamide for life-threatening and corticosteroid resistant hepatic hemangiomas.[rx] The regimens described were 10mg/kg per dose for 3 to 4 days intravenously or orally for 2 or 3 courses.[rx] Cyclophosphamide is an alkylating agent that is thought to block or decrease new capillary proliferation. Reported side effects range from none, to transient myelosuppression and elevated liver enzymes. Serious toxic effects of cyclophosphamide, such as gonadal damage, hemorrhagic cystitis, and secondary malignancies are considered unlikely with a low dose and short term therapeutic use. Cyclophosphamide has not been reported as a single therapeutic agent for the treatment of capillary hemangioma and may be considered suitable adjunct therapy to avoid the toxicity of long-term interferon treatment.[rx]
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Imiquimod – Imiquimod is an immune-response modifier that induces the production of cytokines from keratinocytes and monocytes to cause regression of numerous dermatologic conditions, including warts, superficial basal cell carcinoma, squamous cell carcinoma in situ, and actinic keratosis. Imiquimod has been found successful in treating superficial capillary hemangiomas of the scalp, eyebrow and forehead. This is a new agent with future potential however, safety or efficacicy for ophthalmic use is still under investigation.[rx]
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Systemic propranolol – Systemic propranolol is a new treatment modality introduced by Leaute-Labreze in 2008.[rx] Propranolol is a non-selective beta-blocker that has long been used in the pediatric population for cardiac indications. Leaute-Labreze et al serendipitously observed a dramatic decrease in the size of cutaneous capillary hemangiomas in an infant being treated with propranolol for a cardiac indication. In follow-up report, they observed improvement or regression of the hemangiomas in 31 of 32 patients. One patient discontinued treatment because of wheezing.[rx] Propranolol is now being used successfully for laryngeal and periocular capillary hemangiomas.[rx,rx,rx] The suggested dosage of oral propranolol is 2 to 3 mg/kg/day, divided twice daily, and adjusted for weight changes during the growth of the infant. Beta-blockers do have the risk of exacerbating reactive airway disease, bradycardia, systemic hypotension, and masking of symptoms of hypoglycemia in the infant population.
- Barriers/emollients
- Non-adherent dressings
- Hydrogen peroxide soaks
- Antibiotics
- Becaplermin gel
Surgery
Surgical debulking of the lesion is reserved only for large vision-threatening lesions. As these lesions are irregular and unencapsulated, a complete removal is not possible. However, with careful surgical dissection, the majority of large orbital and eyelid hemangiomas can be successfully treated. Concurrent steroids are injected into any residual hemangioma tissue during surgery.[rx]
Complications
Although most capillary hemangiomas involute over time, some will undergo rapid growth and can cause amblyopia, proptosis with exposure keratitis or optic nerve compression. Ulceration and bleeding may occur but are infrequently seen.
Complications of oral steroids include hypotension, bradycardia, hypoglycemia, bronchospasm, sleep disturbances, diarrhea, and hyperkalemia. These can be overcome by close monitoring at the time of initial administration and proper parental counseling.
Complications of surgical resection include injury to the surrounding tissues like the levator aponeurosis and levator muscle. Orbital capillary hemangioma resection will often result in a residual tumor in the orbit because these lesions are irregular with no capsulation.
References
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