Infantile hemangiomas are the most common benign tumor in children, and their incidence is higher in girls and premature infants.1–3 The tumors usually present as a single sporadic lesion, although multiple and familial forms are not uncommon. Infantile hemangiomas are vascular tumors, which are not usually present at birth but appear during the first weeks of life and grow rapidly over the following months (proliferative phase). The tumor then stabilizes and, after the child's first birthday, begins a slow, gradual regression that can last throughout childhood (involuting phase).4,5 Although it is possible for infantile hemangiomas to regress completely, residual lesions of various types—atrophic scars, redundant fibrofatty tissue, yellowish discoloration, and telangiectasias—persist in a significant number of patients (involuted phase).

Fortunately, because of the benign course described above, most infantile hemangiomas (especially smaller ones and those located in non–cosmetically-sensitive areas) do not require treatment and can be managed by watchful waiting. The tumors should be monitored especially closely during the proliferative phase so that any complications that would necessitate active treatment—such as ulceration, pain, functional impairment, or the possibility of abnormal scarring and disfigurement—can be detected.

The treatment of infantile hemangiomas varies depending on the phase of development, site, and characteristics of the lesion and whether or not visceral involvement or comorbidities are present. Of the treatments currently available, oral propranolol is the first-line option because of its proven efficacy and good safety profile.6–9 Other systemic treatments such as corticosteroids, bleomycin,10 and interferon alfa are also used occasionally. Topical medications such as corticosteroids, β-blockers,11,12 platelet-derived growth factor, and imiquimod13 and various medical and surgical techniques such as sclerotherapy, cryotherapy, radiotherapy, electrocautery, and conventional surgery have also been shown to be useful. Laser treatment also plays an important role.

In this study, we present our experience with the treatment of hemangiomas in various phases of development using dual-wavelength sequential pulses from a pulsed dye laser (PDL) and a Nd:YAG laser (Cynergy Multiplex, Cynosure, Inc., Westford, MA, United States).

Twenty-two patients (20 girls and 2 boys) with infantile hemangiomas, between the ages of 5 months and 13 years, were included in the study. At the time of treatment, the lesions were in different phases of development: proliferative in 2 patients, involuting in 9 patients, and involuted in 11 patients. Five patients had received no prior treatment; the others had received at least 1 of the following: propranolol (n=8), systemic corticosteroids (n=3), surgery (n=4), and PDL (n=9). None of the patients received concomitant treatment while undergoing PDL and Nd:YAG laser treatment. The data are presented by individual patient in Table 1.

The number of laser treatment sessions per patient ranged from 1 to 5 (mean, 2.04 sessions).

Adverse effects were seen in 4 patients (18.18%): mild atrophy (n=2), marked edema and ulceration in a hemangioma on the oral mucosa without subsequent residual scarring (n=1), and hyperpigmentation (n=1). Posttreatment transient purpura and mild edema, which occurred in most patients, were not considered adverse effects but rather expected responses to effective treatment. Table 2 summarizes the complications and improvement observed in each patient.

Table 3 shows the improvement achieved with treatment in the entire group of 22 patients and in the various subgroups (patients with proliferative, involuting, and involuted hemangiomas). Values are expressed as median and IQR.

The difference between the pretreatment and posttreatment values for the entire group of patients was statistically significant (P<.001). The variation was also statistically significant (P<.001) in each of the 3 subgroups.

The ICC among the 4 evaluators was 0.588 (95% CI, 0.385-0.773), indicating moderate, statistically significant agreement.

Figs. 1-4 show patients before and after treatment.

Figure 1.

A, Patient number 4 with an involuting infantile hemangioma on the upper lip before treatment. B, Marked improvement without residual scarring, despite ulceration of the labial mucosa, after 1 treatment session.

(0.28MB).

Figure 2.

A, Patient number 5 with an infantile hemangioma in the early involuting phase. B, Resolution of the lesion after 3 treatment sessions; mild skin atrophy persists in the treated area.

(0.27MB).

Figure 3.

A, Patient number 6 with an involuting infantile hemangioma on the face. B, Good response of the vascular component after 2 treatment sessions.

(0.28MB).

Figure 4.

A, Patient number 22 with residual telangiectasias secondary to hemangiomas on the left upper limb. B, Near resolution of the telangiectasias after 1 treatment session.

(0.35MB).

Treatment of infantile hemangiomas should be tailored to each patient on the basis of factors such as site, functional impairment associated with the lesion, likely future cosmetic impact, phase of development of the hemangioma, and request for active treatment by the patient's family. Accordingly, many infantile hemangiomas do not require pharmacological treatment or surgery and can be managed by watchful waiting, but some eventually do require some sort of intervention. As mentioned above, it is important to consider the phase of development of the hemangioma because not all current treatments are effective in all phases.

In recent years, the treatment of proliferative infantile hemangiomas has been revolutionized by propranolol, which is now considered the drug of choice.6–9 Previously, systemic or intralesional corticosteroids were considered the first-line treatment and other drugs such as bleomycin and interferon alfa were used to treat severe, recalcitrant lesions. Today, these medications are used only in exceptional cases to treat infantile hemangiomas. In some patients—for example, those with hemangiomas of the nasal tip—surgery remains an appropriate option.14

Laser treatment, especially with PDL, has also been used to treat hemangiomas in the proliferative phase. Numerous studies have confirmed the efficacy of PDL, especially for treating superficial hemangiomas, but its usefulness in the treatment of hemangiomas with a prominent deep component is more limited.15–19 Treatment with PDL may cause some adverse effects, including pigmentary changes and, more importantly, the possibility of ulceration and abnormal scarring.20 These complications seem to occur more frequently when PDL is used without a cooling system or to treat segmental hemangiomas. We therefore believe that PDL treatment should be administered by properly trained personnel in order to minimize these complications, especially in patients with segmental hemangiomas. Because of their longer wavelength (1064nm) and, therefore, greater depth of penetration, Nd:YAG lasers are also effective at treating proliferative hemangiomas with a prominent deep component, but their safety margin is smaller than that of PDL.21

In our series, we used dual-wavelength pulses from a PDL and a Nd:YAG laser to treat 2 patients with proliferative infantile hemangiomas with a prominent deep component; marked improvement was observed in both cases. Sequential application of a 595nm PDL followed by a 1064nm Nd:YAG laser has been shown to be effective at treating some capillary malformations resistant to conventional PDL treatment,22,23 cutaneous and mucosal venous malformations,24 angiolymphoid hyperplasia with eosinophilia,25 and infantile hemangiomas.26 The response obtained with sequential application is due to the fact that PDL and Nd:YAG lasers have a depth of penetration of approximately 1mm and 5-6mm, respectively, and therefore reach structures at different dermal layers. Furthermore, PDL is used first. This reduces the oxygenated hemoglobin in the red blood cells to methemoglobin, causing a 3-fold to 5-fold increase in hemoglobin absorption by the Nd:YAG laser and making it possible to set the Nd:YAG laser at a lower fluence, thereby reducing the associated pain and edema.23,27,28 This approach can theoretically reduce the adverse effects associated with the use of Nd:YAG lasers as monotherapy because higher fluences increase the risk of atrophy and unattractive scarring associated with the loss of vascular selectivity.

Sequential PDL and Nd:YAG laser treatment is more painful than PDL as monotherapy. Local anesthesia is required in most patients, and general anesthesia may be indicated in patients with lesions that cover a large area. Topical local anesthetic was used in most of our patients, but a few patients aged less than 1 or 2 years with small infantile hemangiomas required no anesthetic.

The only study that has examined the use of sequential PDL and Nd:YAG laser treatment for infantile hemangiomas yielded promising results.26 The study describes the treatment of hemangiomas in 25 patients. Complete resolution without adverse effects was obtained in 18 patients, complete resolution with slight changes in skin texture or color in 4 patients, and incomplete resolution with possible associated scarring in 3 patients. It is important to note that the patients ranged in age from 3 months to 5 years and that their lesions were in different phases of development. We believe that the results of the treatment of proliferative hemangiomas cannot be considered comparable to the results of, for example, the treatment of telangiectasias in the involuted phase.

Beyond the proliferative phase, the treatment of hemangiomas is somewhat less standardized. Because infantile hemangiomas generally follow a course of progressive involution, a watchful-waiting approach is sufficient, although it should be noted that involution can take several years. Fifty percent of infantile hemangiomas have reached the involuted phase by the time the patient reaches age 5 years. However, residual lesions—ranging from nearly imperceptible alterations to severe disfigurement, plus the associated psychological impact—often persist beyond the involuting phase. Active treatment is therefore required in some cases.

Recent studies support the hypothesis that the use of propranolol beyond the proliferative phase can accelerate the involution of infantile hemangiomas.29 Treatment with PDL or Nd:YAG lasers has also been shown to be useful during the involuting phase. Unfortunately, because most studies on laser treatment for infantile hemangiomas have included patients ranging in age from a few weeks to several years, the real efficacy of laser treatment in patients with lesions in the involuting phase has not been well established. Our series included 9 patients with involuting hemangiomas, all of whom responded well to the treatment. It should be noted that the effectiveness of any therapeutic measure in patients with involuting hemangiomas is difficult to assess. Because the lesions always follow a natural course of spontaneous involution, it can be difficult to determine whether the treatment was responsible for the observed improvement. We believe that, in most of our patients, treatment with dual-wavelength pulses from a PDL and a Nd:YAG laser played a role in the improvement of the lesions because, in many cases, results were evident after only 1 or 2 sessions. Such improvement is unlikely to occur spontaneously in such a short time. Possibly even more difficult to predict is whether the improvement achieved with laser treatment would have eventually been obtained in the long term by spontaneous involution or if residual lesions would have persisted.

Treatment of residual hemangiomas varies according to the predominant component. Surgery may be indicated in cases where redundant fibrofatty tissue persists. In residual lesions characterized by skin texture changes and atrophic scarring, a therapeutic approach similar to that used to treat postacne atrophic scarring may be indicated. In several recent studies, fractional laser treatment has been shown to be effective in the treatment of such lesions.30 However, vascular laser treatment is clearly the first-line treatment in hemangiomas with a predominant vascular component. Lesions of this sort can be effectively treated with PDL, potassium-titanyl-phosphate lasers, or Nd:YAG lasers, all of which are effective in the treatment of telangiectasias secondary to various processes. The selection of one type of laser over the others may be influenced by factors such as vessel thickness and depth, the patient's skin phototype, and the clinician's experience with the various devices.

In our series, involuted hemangiomas were treated in 11 patients, 7 of whom had previously received PDL treatment for the residual vascular component. Because of its good safety profile, we consider PDL to be the first-line treatment for this type of lesion. However, for some lesions, particularly those consisting of large or deep vessels, the response to PDL treatment may be inadequate. We believe that dual-wavelength PDL and Nd:YAG laser treatment is a good alternative in these situations, as the results of this study show.

Despite the promising results, this study had some limitations that should be noted, such as the lack of a control group and the relatively small number of patients treated. Future research should include randomized trials to confirm the effectiveness and safety of the treatment. Another line of future research should explore the possibility of using lasers in combination with other treatments, such as propranolol, to determine whether the results obtained separately with each treatment can be optimized.

In conclusion, we believe that treatment with dual-wavelength pulses from a PDL and a Nd:YAG laser is a good treatment option for infantile hemangiomas in any phase of development when first-line therapies are ineffective or contraindicated.

The authors declare that they have no conflicts of interest.