A, Preterm twin with an erythematous plaque on the neck. B, Same lesion as in panel A after 1 flashlamp-pumped pulsed dye laser treatment. The superficial component resolved, whereas the subcutaneous component proliferated. There was also a transient hypopigmentation of the area. C, Color-coded duplex sonography showing the deep component and the extension of the whole hemangioma. The various colors characterize the low-flow vessels of the hemangioma in the subcutis.
A, An 8-week-old male infant with a cutaneous hemangioma of the scrotum. B, The same patient after 1 treatment with the flashlamp-pumped pulsed dye laser.
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Poetke M, Philipp C, Berlien HP. Flashlamp-Pumped Pulsed Dye Laser for Hemangiomas in Infancy: Treatment of Superficial vs Mixed Hemangiomas. Arch Dermatol. 2000;136(5):628–632. doi:10.1001/archderm.136.5.628
To study in a compared manner the efficacy of flashlamp-pumped pulsed dye laser (FPDL) therapy for superficial and mixed hemangiomas.
Nonrandomized control trial.
Department of Lasermedicine, General Hospital Neukölln, Berlin, Germany.
To investigate variation in response to treatment, a prospective study of 165 children with 225 separate hemangiomas treated with the FPDL was undertaken. Patients were aged 2 days to 7 years; mean follow-up was 5 months.
During a 2½-year period, we administered 332 treatments, for a mean±SD of 2.0±1.1 treatments per patient.
Main Outcome Measure
Patients received therapy until the lesion was almost clear or until the lesion did not respond to treatment. Evaluation was performed by comparing pretreatment and posttreatment photographs. In addition, pathologic flow of vessels and thickness were determined before, during, and after completion of therapy with color-coded duplex sonography.
In the first group of 100 patients with 153 flat cutaneous hemangiomas, 52 hemangiomas (34%) had excellent results; 80 (52%) had good results; and 21 (14%) showed proliferation of the subcutaneous component, although these lesions were flat at first presentation. Of the 54 mixed hemangiomas, 33 (61%) had continued proliferation of the subcutaneous component. The cutaneous component responded to therapy in 21 hemangiomas (39%), whereas the subcutaneous component of the mixed hemangiomas remained unchanged. No lesions in this group involuted completely, and therapy was discontinued because of relatively poor response. Twelve (67%) of 18 patients with superficial hemangiomas in the involution phase had excellent results and 6 (33%) had good results.
Treatment with the FPDL is effective and may be the treatment of choice for superficial cutaneous hemangiomas at sites of potential functional impairment and on the face. Hemangiomas with a deep component do not benefit from FPDL treatment because the efficacy of the FPDL is limited by its depth of vascular injury. Furthermore, early therapeutic intervention with the FPDL may not prevent proliferative growth of the deeper or subcutaneous component of the hemangioma despite early intervention.
HEMANGIOMAS ARE common benign vascular tumors that are present at birth in 2% to 3% of newborns1 and in up to 22% of preterm infants weighing less than 1000 g.2 Hemangioma has a female-male preponderance of 3:1.3 Lesions initially appear as a white or pink macule, a port-wine stain–like lesion, or a telangiectasia with surrounding vasoconstriction (prodromal or initial phase). Some stay flat, elevating only slightly above the precursor stage, whereas others grow (proliferation phase) to become truly gigantic. Hemangiomas have been classified as cutaneous, subcutaneous, or mixed. Their color intensity essentially depends on their depth and spread and the lumina of the vessels involved, but there may be fluctuation due to localization, state of excitement, and temperature.
Although all regions of the body can be affected by hemangiomas, 60% to 70% are localized on the head. The most common complications of hemangiomas are ulceration and secondary infection, bleeding, disfigurement (especially with facial lesions), and ophthalmic problems related to periorbital lesions; furthermore, an airway hemangioma might produce obstruction and respiratory failure.
Hemangiomas are characterized by a proliferation growth phase followed by slow, inevitable regression (involution phase) between 1 and 10 years of age. Although hemangiomas resolve, lesions persist in 35% to 50% of children who begin school. Even after spontaneous involution of the lesions, 15% of children have residual skin changes, including depigmentation or hyperpigmentation, telangiectasia, atrophy and wrinkling of the skin, and cutaneous depression. If skin changes occur, remaining changes of the skin may correspond to the largest size of the hemangioma.4 However, spontaneous regression is no guarantee of a satisfactory cosmetic result, as is often presumed.
Because these lesions may involute spontaneously, allowing for spontaneous regression remains a viable therapeutic option. Alternative treatments have included radiation therapy, electrosurgery, cryosurgery, surgical excision, sclerotherapy, embolization, and drug therapy. In view of the potential adverse effects, these treatments have not generally been advised for patients with cutaneous hemangiomas. The quest for a therapy that eliminates hemangiomas before development of complications and without systemic or cutaneous adverse effects has been difficult. The flashlamp-pumped pulsed dye laser (FPDL) has been demonstrated to effectively and safely treat cutaneous vascular lesions like port-wine stains and telangiectases in children while significantly minimizing any cutaneous adverse effects. Several clinical trials5-9 with the FPDL have been reported. Using the FPDL, an early and careful therapy of hemangiomas has become possible so that hemangiomas can be treated in the initial or prodromal stage to avoid enlargement. The response of cutaneous hemangiomas to FPDL treatment has recently been described.10,11 We studied in a compared manner the efficacy of FPDL therapy for superficial cutaneous and mixed hemangiomas.
A total of 165 children aged 2 days to 7 years with 225 hemangiomas were treated with the FPDL at the Department of Lasermedicine, General Hospital Neukölln, Berlin, Germany, between July 1996 and December 1998: 113 girls (68%) and 52 boys (32%). Forty-one patients were preterm infants; we started treatment when the children weighed more than 1800 g. Six patients were twins and 1 was a triplet.
Although most lesions (n=87) were localized to the face and neck, 60 patients had a lesion on the extremities, 59 had a lesion on the trunk, and 19 had a lesion on the anogenital region. Eight lesions were ulcerated at presentation.
The 165 patients were divided into 3 groups: 100 patients with 153 flat cutaneous hemangiomas, 47 with 54 mixed cutaneous-subcutaneous lesions, and 18 with 18 superficial hemangiomas in the involution phase.
Of 153 flat hemangiomas, 74 were clinically early hemangiomas (48%) in the initial phase that looked like a faint macular pink patch, with a patient age range of 2 days to 8 weeks; 48 (31%) were actively proliferative hemangiomas; and only 31 (20%) were matured hemangiomas in the more well-developed phase, that do not develop beyond this flat stage. They usually looked bright red and nodular. In the group with actively proliferative flat hemangiomas, the average patient age was approximately 14 weeks (range, 10 weeks to 7 months). Those with matured hemangiomas were aged 11 weeks to 9 months.
In the group with mixed hemangiomas, patients were aged 4 weeks to 10 months. Patients with superficial hemangiomas in the involution phase were aged 10 months to 7 years. Four were younger than 1 year and only 2 were older than 7 years. All these lesions were slow in regressing and occurred in a cosmetically or functionally prominent area. Mean follow-up for each group was 5 months.
Pathologic flow of vessels and thickness were determined before, during, and after completion of therapy with a color-coded duplex sonography system with a linear array applicator of 7.5 to 9.0 MHz (Sonoline Elegra; Siemens Aktiengesellschaft, Erlangen, Germany). Furthermore, photographs were taken of all patients before and after each treatment.
Informed consent was obtained before the procedure, and risks and benefits were explained to the patients' parents.
We used the FPDL (Carl Baasel-Lasertechnik GmbH, Starnberg, Germany) with the following settings: a wavelength of 585 nm and a pulse duration of 300 microseconds. The laser beam was transmitted down at 1-mm fiber with the use of a convex lens and was focused directly on the skin surface with a 5-mm spot beam. Energy fluences ranged from 5 to 7 J/cm2, and its use varied according to the age of the patient and the anatomical location and thickness of the lesion. Energy fluency was frequently reduced over the eyelids, hands, scrotum, and gluteal region. Treatments are performed with a maximum spot overlap of 20% to 30%.
The high pulse peak power of the FPDL disrupts the vessels. Immediately after treatment, the treated area turned blue-lilac (purpuric), with surrounding erythematous flare; this took 7 to 14 days to resolve. Some edema, especially in the periorbital area, was possible. If blanching or graying of the epidermis occurred during application, energy fluences were reduced to avoid blistering of the epidermis. After treatment, the treated areas were covered with panthenol ointment. In case of blistering or crusting, patients' parents were instructed to cleanse the area with povidone-iodine solution. Furthermore, we instructed parents to keep their children's fingernails short or to have the children wear gloves to avoid trauma to the treated areas. Patients were then evaluated at 2 to 4 weeks, and, depending on the degree of response, the entire lesion was then treated again, usually 4 weeks after the first session.
Because these lesions are usually small in diameter and few in number, 122 children (74%) generally tolerated the treatment well without anesthesia. Infants older than 1 year (8% of patients) had topical anesthetic cream (Eutectic Mixture Topical Anesthetics; Astra Pharmaceutical, Oslow, Sweden) applied for 1½ hours under occlusion before laser treatment. General anesthesia was helpful for children with extensive hemangiomas over a large dermatome and hemangiomas of the periorbital area, especially if the eyelids were treated. Therefore, an eye shield was used to protect the globe. Thirty patients (18%) required general anesthesia.
Results were considered to be "excellent" when the hemangioma had completely cleared, "good" when involution of the tumor was slower or lightening was not complete, and a "failure" when the hemangioma remained relatively unchanged or the lesion showed further enlargement. Patients with treatment failure received further therapy with the Nd:YAG laser at 1064 nm with the following settings: a power of 25 to 46 W, a spot size of 5 mm, and application in continuous mode. Highly sufficient protection of the skin was provided by clear ice cubes placed directly on the skin, whereby the laser beam was applied directly through these ice cubes and the coagulation depth could be increased up to 10 mm.
We administered 332 treatments, for a mean±SD of 2.0±1.1 treatments per patient. Responses were considered to be excellent in 64 hemangiomas (28%), good in 107 (48%), and failures in 54 (24%) (Table 1).
Of 153 flat hemangiomas in 100 patients, 52 (34%) had excellent results and 80 (52%) had good results. Of 54 mixed hemangiomas in 47 patients who received FPDL treatment, 21 (39%) had good response to treatment and 33 (61%) failed. Of 18 superficial hemangiomas in the involution phase in 18 patients, 12 (67%) had excellent results and 6 (33%) had good results.
The 153 flat hemangiomas showed no pathologic flow into the subcutis in color-coded duplex sonography before FPDL treatment. Thus, patients with flat cutaneous hemangiomas were more likely to have an excellent response (34%). These lesions showed total lightening. The mean±SD number of treatments needed to achieve complete involution was 1.6±1.1 (range, 1-5); 52% of hemangiomas had good results after 1.4±0.7 treatments. Greater degrees of regression were seen with increased numbers of treatments.
Early or initial hemangiomas lightened 41% compared with 21% for actively proliferative hemangiomas and 52% for the flat matured hemangiomas and needed 2.1±0.9 treatments compared with 1.4±0.9 treatments for actively proliferative hemangiomas. Of 74 initial hemangiomas, only 13 (18%) showed no limitation of proliferation into the subcutis compared with 8 (17%) of the 48 actively proliferative hemangiomas, and further therapy with the Nd:YAG laser was desired. In all of these cases with proliferation of the deep component, coloration by perfusion in the color-coded duplex sonography was observed (Figure 1).
Of 54 mixed hemangiomas, all showed capillarization and hyperfusion in the subcutis up to a depth of approximately 4 mm in color-coded duplex sonography at presentation.
None of the mixed hemangiomas completely cleared; 33 (61%) had continued proliferation of the subcutaneous component. The cutaneous component responded to therapy in 21 hemangiomas (39%), and the subcutaneous component of these mixed hemangiomas remained unchanged. This was confirmed by color-coded duplex sonography. The number of treatments in these lesions was 1.6±0.8 (range, 1-5). Compression of thicker lesions with a glass slide to assist in laser penetration did not increase the effectiveness of therapy. In 61% of the thicker lesions, further therapy with the Nd:YAG laser was performed with good results.
The greatest degree of effectiveness was noted in superficial hemangiomas in the involution phase: 12 (67%) of 18 patients had complete involution and clearing of their lesion after 1.9±1.2 treatments (range, 1-4). In 6 patients (33%), lightening was not complete after 1.6±0.6 FPDL treatments. Greater degrees of regression were seen with increased numbers of treatments.
No textural changes after treatment were seen in treated skin in 206 hemangiomas (92%), whereas 8 (4%) had small, isolated, scars in areas ulcerated before laser treatment. Hyperpigmentation occurred in 2 hemangiomas (1%) but resolved spontaneously in 7 weeks; hypopigmentation occurred in 9 hemangiomas (4%). Normal skin color returned spontaneously within 8 weeks in all patients; there were no permanent complications.
The FPDL is the first laser specially designed to treat cutaneous vascular lesions and the first laser to eliminate these lesions predictably without producing a scar. It is characterized by a selective destruction of blood vessels by matching the wavelength of light absorbed by hemoglobin into the vessels and by using an exposure time less than the calculated thermal relaxation time (1-10 milliseconds) for the blood vessels.12 An exposure time of 1 millisecond or less was advocated to confine that heat to the vessel to decrease the risk of heat diffusion, which can cause scarring.
The depth to which light penetrates tissue is also a critical limiting factor in laser treatment and is directly proportional to the wavelength of the light. For the FPDL adjusted to 585 nm, the depth of penetration for 50% of the energy is calculated to be 0.8 mm,12 a prediction confirmed histologically in laser-treated skin.13 Because the dermis of facial skin is approximately 0.6 mm deep in children14 and approximately 0.9 mm deep in adults,15 the FPDL provides adequate penetration for cutaneous vascular lesions.
The FPDL has proved to be a safe and effective treatment modality for port-wine stains,5,8,9,16 especially in treating small vessels found in childhood port-wine stains.
Since the study by Sherwood and Tan10 of the successful treatment of a hemangioma of the finger with the FPDL, several authors have reported equally successful results.11,17 Hohenleutner and Landthaler18 treated 198 patients with hemangiomas, and 74% of these patients with initial hemangiomas had a 75% or greater lightening of their lesions with no evidence of permanent scarring. Good to excellent results (complete regression or >75% lightening) have been noted in 61% of these patients with cutaneous hemangiomas and 42% with mixed hemangiomas. Landthaler et al19 described 28 patients with a total of 37 hemangiomas treated with the FPDL. In that study, 29 hemangiomas were classified as cutaneous and 8 as mixed. Of these patients, a good or excellent response with complete regression of the hemangiomas was achieved in 60%, and in deep-seated or mixed hemangiomas regression was seen in 40%. All 4 patients with mixed hemangiomas were considered treatment failures; further therapy with the Nd:YAG laser was performed.
An earlier study by Garden et al20 involved 24 patients with 33 hemangiomas. Patients were aged 2 weeks to 7 months. In 18 of 25 lesions that were 3 mm or less in elevation lightened in therapy and flattened in thickness in 93.9%, and mixed hemangiomas that were 4 mm or more in thickness lightened in 85.7% but showed less diminution in thickness.
This study of 225 hemangiomas compared the response of flat cutaneous hemangiomas with that of mixed cutaneous-subcutaneous hemangiomas: flat hemangiomas (Figure 2) responded much better to the FPDL treatment and involuted more completely than did mixed hemangiomas. We saw a greater percentage of regression if early or initial cutaneous hemangiomas were treated than in actively proliferative cutaneous hemangiomas. Also, actively proliferative cutaneous hemangiomas did not regress as much as some of the matured cutaneous hemangiomas. On the other hand, 13 (18%) of 74 initial hemangiomas showed proliferation of the subcutaneous component, although these lesions were flat at first presentation and no pathologic vessels were found in color-coded duplex sonography before FPDL treatment. So, in our experience, FPDL treatment could not always prevent proliferation of the deep component, even in initial flat hemangiomas.
Even mixed hemangiomas lightened, although they persisted. The subcutaneous component of mixed hemangiomas did not appear to respond, and further therapy with the Nd:YAG laser with continuous surface cooling with ice cubes was performed with good results.
All these studies demonstrated a better treatment outcome in flat cutaneous hemangiomas. Treatment of mixed hemangiomas has been the source of some controversy in the literature. Garden et al20 suggested that early treatment of hemangiomas may prevent proliferation of the deep component and hasten involution of superficial hemangiomas. Conversely, Ashinoff and Geronemus21 reported 4 cases in which the deep component of the hemangioma continued to proliferate after treatment with the FPDL, whereas the superficial component resolved. Ashinoff and Geronemus11 showed that the thicker the lesion at presentation, the less effective was FPDL treatment, which was not surprising given the limited degree of vascular injury caused by this laser. Berlien et al22-24 reported better results in deep hemangiomas with the Nd:YAG laser (1064 nm) when a coagulation depth of 10 mm can be reached and highly sufficient protection of the epidermis is provided by continuous ice cube cooling.
Sometimes it is difficult to predict whether there will be a superficial and deep component of the hemangioma or only a superficial component. In our experience, a color-coded duplex sonography is helpful. It allows precise measurement of the diameter of single vessels, the thickness, and the extension of the whole hemangioma. Those reproducible flow measurements may be performed and compared during follow-up together with the B-scan imaging.
Because of results we have seen from FPDL treatment, we recommend that FPDL for the treatment of hemangiomas be reserved for use in carefully selected patients, ie, those with cutaneous and flat hemangiomas at sites of potential functional impairment (hands, feet, or anogenital region) and especially on the face. Furthermore, hemangiomas should be treated with the FPDL as soon as possible, even in the initial or early phase, before the lesions reach an exponential growth phase, and the limited depth of vascular injury of the FPDL is unlikely to effect any improvement in decreasing the size of the lesion. Because flat hemangiomas in the superficial cutaneous and involutionary groups responded best, we believe it is only a factor of whether the FPDL can sufficiently penetrate the total hemangioma. So, the depth of the hemangioma is relevent. Subcutaneous or mixed hemangiomas do not benefit from FPDL treatment because the efficacy of the FPDL is limited by its depth of vascular injury (1-2 mm), and mixed hemangiomas might extend far beyond this depth into the subcutaneous tissue.
Also, cutaneous hemangiomas during the involution phase benefit from FPDL treatment. Many of these lesions are slow to resolve and can be present in a cosmetically or functionally prominent area.
As with the treatment of port-wine stains, the incidence of adverse effects from FPDL treatment of hemangiomas is small, thus making the benefit-risk ratio high.
Accepted for publication December 14, 1999.
Reprints: Margitta Poetke, MD, Abteilung für Lasermedizin, Krankenhaus Neukölln, Rudower Strasse 48, D-12351 Berlin, Germany.