5.Natural History
9. Table 1     




"Our whole attitude to the treatment of strawberry naevi must be based on the knowledge of their invariable tendency to spontaneous regression"

W.A. Lister, MD

Any decision to treat a patient’s condition must be weighed against the natural history of that disease or condition. When discussed in reference to hemangiomas this natural history is quite good for the majority of lesions. It is estimated, however, that up to 10% of hemangiomas can cause complications requiring active treatment. These include those patients for which involution has not afforded a satisfactory result. Other indications for treatment include cardiac failure, airway, rectal or auditory obstruction, ocular complications, coagulopathy, psychosocial concerns, ulceration or infection. The practitioner should recognize the concerns of the parents but should keep the child’s best interests in mind. It is never a good idea for the physician to allow parental pressure to push him or her into a treatment plan that is not clinically appropriate. In cases where clinical intervention is taken, informed consent is mandatory and can prevent costly lawsuits.48

Recommendations can be made even if the goal is to "wait and watch" for natural involution of the hemangioma. Parents are encouraged to take photographs and they are frequently taken in our clinic so that a series of pictures can be compared between visits. Showing the family a series of pictures of hemangiomas that have involuted without specific treatment is also reassuring. An effort should be made to give emotional and psychological support to the parents of an affected child particularly if no active treatment is recommended.31,32 Periodic reevaluation is indicated even if the initial recommendation is to "wait and watch".

Low risk treatments include compression therapy.49-52 Compression therapy, using self-adhesive wraps, has been effective in the treatment of acral hemangiomas and other compression devices have shown impressive results when treating tumors located in other locations. Occlusion with a polyurethane film can be used to decrease the pain and speed the healing of ulcerative hemangiomas.53 Topical antibiotics and lubricants are also useful when a hemangiomas become ulcerative. Systemic antibiotics are usually necessary if overt infection is present. The use of high potency topical steroids has been reported but has not enjoyed widespread usage.54

Intralesional corticosteroids are frequently used by ophthalmologists for treatment of periocular hemangiomas and can be used for hemangiomas located in other locations.55-61 Multiple injections are usually necessary, often utilizing general anesthesia if periocular tumors are treated. Reported complications of this therapy include skin necrosis, atrophy or a cushinoid appearance.56 Occlusion of the central retinal artery resulting in either transient or permanent blindness can be a rare complication of intralesional steroid therapy.59 Bleomycin is another intralesional agent that has been reported to be useful in a small trial of patients with hemangiomas.62 Massage may be used prior to surgery or dilation for hemangiomas that occlude the lacrimal drainage system.

Systemic corticosteroids were first noticed to shrink hemangiomas over 30 years ago.63 Although their mechanism of action is not entirely understood, vasoconstriction, inhibition of angiogenesis, and a decrease in mast cells and levels of estrogens could all contribute to the results seen with systemic corticosteroid treatment. Extensive facial hemangiomas or those located in critical areas, such as the periorbital area, are often treated with systemic corticosteroids. Ulcerated or infected hemangiomas may also be considered for corticosteroid treatment. The presence of high output cardiac failure or platelet trapping associated with the Kasabach-Merritt phenomenon are also indications for corticosteroid use.

It should be stressed that systemic steroids are most effective during the proliferative phase, which means most children treated will be less than one year of age. An initial dosage of 1-3 mg/kg of oral prednisone is commonly given in one morning dose. Hemangiomas should respond within 7-10 days. If they do not respond, the corticosteroid should be stopped abruptly. If response is seen then tapering to the lowest effective dose is recommended. Rest periods of 2-4 weeks are often given between 4-6 week courses. Common side effects include gastrointestinal upset, sleep disturbance, temporary growth retardation, decreased appetite, and transient facial edema.64 More limiting, and fortunately uncommon, side effects include otitis media, pneumonia, sepsis and hypertension.

Interferon alpha-2a is a potent inhibitor of angiogenesis that has been used successfully in patients with aggressive hemangiomas that are refractory to systemic corticosteroid therapy.65,66 Common side effects include neutropenia and fever. A subcutaneous dose of up to 3 million units/m2 of body surface area is utilized. A 10% incidence of significant neurologic toxicity, predominantly spastic dysplegia, has been reported in patients treated with interferon alpha-2a.66 While toxicity usually resolves with discontinuation of treatment, neurologic abnormalities may persist in some patients. Naltrexone, a long-acting opioid antagonist has been used to treat the neouropsychiatric side effects in some patients taking interferon alpha-2a.67,68

Various lasers have been used to treat hemangiomas. One of the strongest indications for laser use is the presence of ulceration. Ulcerative hemangiomas respond nicely to the pulsed dye laser if in fact the12a-b.jpg (14832 bytes) ulcerative component of the hemangioma is limited and the rate of proliferative growth is mild.69,70 Ulcerations in rapidly proliferating hemangiomas often do not respond to pulsed dye laser photocoagulation. Recent advances in the use of the pulsed dye laser with longer pulse widths and wavelengths as well as the addition of dynamic cooling have allowed for the use of higher energy fluences with more rapid and complete response.

In addition to ulcerative lesions, the pulsed dye laser can be used effectively in the management of superficial and moderately deep hemangiomas during the proliferative phase of growth as well as during the involutional phase.71,72 The use of this vascular specific laser is helpful during the proliferative phase in that superficial proliferative growth can be significantly minimized or halted (Figure 12 a,b).

13a-c.jpg (16833 bytes)Pulsed dye laser photocoagulation works even better during the involutional stage where rapid responses are sometimes seen. Treatment during the proliferative stage of growth should occur at two to three week intervals in an effort to avoid re-growth between treatment sessions. Pulsed dye laser is also effective for treatment of residual telangiectasia caused by incomplete involution (Figure 13 a,b,c).

Thicker hemangiomas and those with a subcutaneous component do not respond as well to laser treatment because of a limited penetration of laser light.73 Intralesional laser therapy is a promising technique that delivers laser light to deeper areas of the hemangioma and may be useful for subcutaneous and deeper tumors.74,75

Carbon dioxide lasers are utilized in the treatment of small symptomatic proliferative laryngeal hemangiomas in an effort to maintain a patent airway but can cause scarring and tracheal stenosis when circumferential or large lesions are treated.76 The carbon dioxide laser can be use in a continuous mode to vaporize those laryngeal tumors that have not regressed in a satisfactory manner. Because of the risk of scarring with laser treatment, tracheotomy with or without systemic corticosteroids is the mainstay of therapy for large or circumfrential laryngeal hemangiomas.

Cryosurgery enjoyed widespread use in past times and has been recently revived for the treatment of hemangiomas, particularly early superficial cutaneous lesions.77 It is postulated that selective necrosis of vascular tissue can occur after freeze-induced thrombosis. Repeated treatments at 2-3 week intervals are required by an experienced operator to avoid scarring or pigmentary changes.

Indications for surgical excision can include hemangiomas with incomplete resolution, severe disfiguring facial lesions, those located in the periorbital area, nose, mouth, upper airway, or ear canal or those lesions that pose a threat to the child’s health. Patients with hemangiomas of the lip or nasal tip frequently undergo surgery prior to starting school because of the slow involution and high visibility of hemangiomas in these locations.78 Surgical treatment of selected periocular tumors is a resonable alternative to systemic or intralesional steroids.79 A more controversial area is the removal of smaller facial hemangiomas that may involute with good results if given enough time. Some surgeons remove these lesions at an early age to spare the patient and the family anticipated psychosocial injury.

Radiation was a common treatment for hemangiomas 50 years ago, before the favorable natural history of most hemangiomas was publicized. The use of ionizing radiation has the disadvantage of long term sequelae and should not be used routinely for hemangiomas.80 Despite its disadvantages, irradiation remains a treatment option for life threatening hemangiomas or vascular tumors that are refractory to aggressive medical and/or surgical therapy.81 Most of these patients will have Kasabach-Merritt phenomenon or multiple hemangiomas with visceral involvement.

Embolization of hemangiomas can be utilized alone, or more commonly, in conjunction with pharmacological or surgical therapy.82 A common indication is hepatic hemangiomas. After angiography, absorbable or permanent particles are introduced into feeding vessels under fluoroscopic guidance by an experienced surgeon or radiologist. Complications include cerebral vascular accidents and skin necrosis caused by accidental or overzealous obstruction of some arteries. Embolization differs from sclerotherapy, in which ethanol is commonly used as a sclerosant. Injection of ethanol does not require angiography and complications, including cerebral vascular accidents, are unlikely.

The treatment of the Kassabach-Merritt (KM) phenomenon deserves special mention because of the numerous therapies that have been tried and the experience that no treatment or combination of treatments produces a uniform response in the treatment of this condition. As mentioned previously, most patients with KM phenomenon have borderline malignant tumors rather than common hemangiomas.10 Pharmacologic therapy with corticosteroids and interferon is frequently utilized as first line therapy.83 Because of the variable response that is frequently seen, cytotoxic agents, such as vincristine and cyclophosphaminde can be tried.84,85 To counter the hematologic effects of the KM phenomenon, pentoxifylline, epsilon-aminocaproic acid, and transexamic acid have been prescribed.86-88 Heparin is contraindicated and platelet transfusion may enhance the bleeding associated with the Kasabach-Merritt phenomenon.

Interventional strategies, such as embolization and surgical resection are effective, but sometimes not technically feasible. If pharmacologic therapy is not successful and surgery is not feasible, then radiation can be utilized. Pneumatic compression can be effective in a subset of patients but cannot be applied in all locations. Aggressive and innovative management of these patients is warranted because of the high mortality of the condition.10

While there have been remarkable advancements in the classification and treatment of hemangiomas there has been little insight into the pathogenesis of these tumors over the last half century. In past times the theory of "maternal impression" prevailed.89 According to this view, it was postulated that the thoughts and desires of the mother concerning blood or certain red fruits caused hemangiomas to occur. More recently theories concerning failed embryonic development or angiogenesis dysfunction are popular. The challenge for the next generation is not only to improve upon the treatment of patients with this condition but to uncover the mystery of their causation.

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