11.5 Modalities of Treatment

Application of a potent topical steroid (0.05% clobetasol propionate cream) has been shown to stabilize or shrink small superficial lesions [18]. It has been used instead of intralesional injection in lesions involving the visual axis. It is felt to cause a somewhat slow regression of the lesion, and the improvement in anisometropia is limited [7, 9, 18].

observed within 1–2 weeks of treatment. Medication is maintained at this dose for 4–6 weeks, then gradually tapered according to the clinical evolution. Rapid discontinuation of the drug can be followed by rebound growth; treatment usually has to be maintained until the end of the proliferative phase, which often means several months of treatment. Oral corticosteroids are not e ective past the proliferative phase. Side e ects of corticosteroids are well known and include cushinoid appearance, irritability, gastrointestinal disturbances, hypertension, transient growth delay, and potential adrenal suppression [20]. There is some concern about possible neurologic complications, especially in premature infants [23–25].

Kushner first reported on intralesional injections of a mixture of 40 mg/ml Kenalog mixed with 6 mg/ml Celestone. The response is usually rapid, occurring in less than 2 weeks and with continuous regression for up to 2 months. Injection could be repeated. Many of these lesions were of small size, for which observation and specific management of the anisometropia and amblyopia are often achieved successfully. But, a study by Weiss and Kelly showed that astigmatism induced by the hemangioma could be reduced by 63% after corticosteroid injections [43].

More recently, this modality of treatment has lost popularity. Complications are significant and can be serious. When larger lesions are treated or in small infants, adrenal suppression can occur and has been documented. Eyelid necrosis has been seen, and one of us has seen such a case with secondary scarring. In other instances, atrophy of the soft tissue along the lymphatic channels draining the area of injection has been reported, as well as skin depigmentation in the area of treatment. Some of these side e ects can be reversible. Most worrisome have been the reports of embolization of the central retinal artery with secondary occlusion while injecting an IH. We are aware of another unreported case in our institution, and sporadic similar cases have been reported after eyelid injection and even intranasal injections [14, 41, 44, 46].

11.5.1.3Oral Corticosteroids

Oral corticotherapy is considered the “gold standard” in the treatment of complicated IH [6–8]. Usually, oral prednisone or prednisolone is initiated at a dose of 2–3 mg/kg/ day, given as a single daily morning dose. A positive response to treatment is either shrinkage or cessation of growth of an actively proliferating lesion. This is usually

11.5.2Interferon-Alfa

Interferon-alfa, a potent angiogenesis inhibitor, has been shown to be e ective in treating complicated IHs and was quite popular in the early 1990s [15, 38]. E ective doses are 1–3 million U/m2 given by daily subcutaneous injections. Initial enthusiasm was dampened by the observation of serious neurotoxicity in the form of spastic diplegia, occurring in up to 20% of infants treated in some series [4].This complication can be reversible if detected early and medication stopped. Currently, interferon-alfa use is restricted to potentially life-threatening or severe function-threatening IHs nonresponsive to systemic corticosteroids. This treatment should only be given by experienced physicians and requires close follow-up, especially regular neurologic evaluations to detect possible neurotoxicity at an early stage (Figs. 11.4 and 11.5).

Fig. 11.4 Toddler with rapidly growing infantile hemangioma progressing despite systemic steroids

Fig. 11.5 Lesion of same child showing rapid regression after interferon-alfa

11.5.3 Vincristine

Vincristine is another second-line option for large,endangering, corticosteroid-resistant IHs and appears to present less neurotoxicity than interferon-alfa [16, 37]. It has gained popularity after reports of its e ectiveness in the treatment of other vascular tumors associated with Kasabach–Merritt phenomenon. Again, this medication requires a collaborative approach, usually with a hematooncologist. One of the drawbacks is the necessity of a central venous line because of the highly caustic nature of this medication. Studies are ongoing to determine its precise role in this setting.

11.5.4Laser

The use of pulsed-dye laser (PDL) in the treatment of proliferating IH is controversial [5, 26]; it can be considered in very superficial lesions because the depth of penetration of PDL is less than 2 mm. This treatment, even if performed early, does not prevent the potential development of an associated deeper component in many cases [2]; it can also induce ulceration or make it worse, resulting in permanent scarring [45]. Paradoxically, it can be

useful in the treatment of ulcerated IHs when topical therapies have failed. PDL is also e ective for the residual telangiectasia and erythema of an involuted IH.

11.5.5Embolization

The vascular tree of the periocular area, especially in toddlers, does not yield itself to selective embolization, especially when large lesions with complex vascularization are present. Smaller localized lesions that could theoretically be treated that way are better handled with modalities that are simpler and less complication prone. Complications from embolization procedures include risk of blindness from optic nerve or retinal vasculature thrombosis [9].

11.5.6Surgery

Surgical resection has been advocated by many authors. Lesions amenable to surgery are lesions that are usually localized in a preseptal fashion or situated anterior in the orbit and that do not involve the skin to avoid scarring and necrosis of the skin. Indications for surgery are lesions unresponsive to medical therapy, including, in some publications, intralesional injection of steroid. Surgical interventions have been advocated early by some authors to allow regression of the astigmatism [1, 19, 29]. Complications occurred in four cases of ten patients; complications consisted of wound infection, need for additional surgery in two cases, and entropion with trichiasis in one [29].

Surgery certainly has a role to play in the late correction of a partially regressed lesion after or late in the involution phase when the lesion has undergone fatty changes. Often, superficial lid changes with loss of its natural elasticity may warrant surgery to correct a persistent cosmetic blemish. New modalities of treatment, including the use of beta-blockers, may reduce the need for surgery in the proliferative phase while still avoiding the complications associated with prolonged use of steroids or with intralesional injections. Many surgeons will intervene to correct residual changes late in the involution phase except in very specific cases. Early surgical excision can reasonably be considered in small, pedunculated hemangiomas that would likely result in significant cosmetic defect after natural involution. Circular excision with purse-string closure is a technique that results in smaller scars than the traditional lenticular excision [33]. Excision of any disfiguring residual lesion before starting school is desirable when possible to avoid psychological sequelae.

11.5.7Beta-Blockers: A New Promising Modality of Treatment

A new treatment option has been proposed in the form of 11 the nonselective beta-blocker propranolol [27]. This was discovered fortuitously, initially in corticosteroid-failure patients. The initial report of 11 infants with severe or disfiguring IH treated with propranolol at 2 mg/kg/day showed impressive results with minimal side e ects. In all patients, 24 h after the initiation of treatment, a change in the color of the lesion was observed along with softening of the mass. In five cases for which ultrasonography was done, an objective regression of the lesion was observed. Improvement leading to flattening of the lesion was noted with continued treatment. Since this was published, many centers have started using this medication with various protocols, often initiating treatment in a hospital setting to monitor vital signs; in the outpatient setting, beginning medication at a lower dose (i.e., 0.5 mg/kg/day) and gradually increasing up to 2 mg/kg/day with close monitoring of blood pressure and pulse is another option. The optimal dosage and frequency of administration of propranolol for IH is still not well established, and additional studies

are necessary before this medication can be recommended on a widespread basis. At this time, this is still an o -label use. Contraindications include bronchospasm/asthma, congestive heart failure, bradycardia, or hypotension. Hypoglycemia can occur, especially in the very young infant. There is concern that propranolol, because of its vasoconstrictive e ect, could provoke complications in the setting of cerebrovascular anomalies in patients with PHACE syndrome; it is thus recommended to obtain an MRA in infants with facial segmental IHs to evaluate the cerebral arteries before considering this treatment option. Propranolol, however, appears to be an extremely promising new treatment option with a better safety profile than interferon-alfa or vincristine and potentially might become the first-line treatment for complicated IHs. As with other systemic treatments for IHs, a multidisciplinary approach is optimal. The mechanism of action of propranolol in IHs is not well understood but may include vasoconstriction, explaining the very rapid color change and softening of the IH after initiating treatment; propranolol has also been shown to decrease the expression of VEGF and bFGF genes in vitro as well as to trigger apoptosis of capillary endothelial cells [28] (Figs. 11.6–11.11).

Fig. 11.6 Photograph of a toddler with continued growth of an IH despite systemic corticosteroids

Fig. 11.7 Necrosis of portion of the involved ear occurred despite initiation of steroids

Fig. 11.8 Marked regression of the lesion 6 weeks after initiation of propranolol at a dosage of 2 mg/kg/day

Fig. 11.10 Large, rapidly growing IH involving the lower lid and the cheek causing visual axis blockage

Fig. 11.11 Marked change in color, flattening, and softening of the lesion 3 weeks after initiation of propranolol, allowing for clearing of the visual axis. No other treatment was used in this patient

Fig. 11.9 Further regression of the abnormal vessels is seen at 10 weeks after initiation of the treatment. Gradual tapering of steroids was initiated 4 weeks after the initiation of propranolol

Summary for the Clinician

■Systemic steroids are the gold standard for large IHs for which systemic treatment is necessary.

■Interferon-alfa is used only in severe selected cases because of its potential for severe side e ects.

■Intralesional injection should be used cautiously.

■Surgery is indicated mainly in localized lesions or to correct anatomical defects in the involutional phase.

■Propranolol o ers a new and promising modality of treatment with potentially fewer systemic complications than the available alternatives.