Biomedical Engineering Reference
In-Depth Information
lipomyelomeningocele, vesicorenal abnormalities, imperforate
anus, and skin tags, the so-called PELVIS syndrome (150).
Multiple cutaneous IHs (i.e., hemangiomatosis) may portend
visceral involvement (151,152). Importantly, the presentation
of a patient with a rapidly enlarging vascular lesion in asso-
ciation with coagulopathy, thrombocytopenia due to plate-
let trapping, and microangiopathic hemolytic anemia (the
so-called Kasabach-Merritt syndrome) was historically attrib-
uted to IHs; it has since been demonstrated that this clinical
picture is much more closely associated with different vascular
tumors, namely, tufted angioma and kaposiform hemangioan-
dothelioma (153).
Ulceration remains the most common complication of IHs,
with an estimated incidence of between 5% and 13% of all
lesions (154). It is also a frequent reason for referral to special-
ists. While the pathogenesis of ulceration is unknown, it is
clear that ulceration occurs most commonly in the prolifera-
tive phase, and it tends to more frequently affect hemangiomas
located in areas of frequent trauma (e.g., occipital scalp, lips,
genitals, perineum, perianal region, and others) or in moist
intertriginous sites (e.g., axilla or neck). Likewise, ulceration
may be associated with certain clinical risk factors (e.g., rapid
growth of lesions, trauma, contact with irritant body fl uids
such as saliva or stool/urine) (155) and as a side effect of treat-
ment, such as laser, corticosteroids, or imiquimod. Conservative
treatment with topical and/or oral treatment (e.g., beta-
blockers, corticosteroids, and others), excellent local wound
care, infection prevention, and effective pain management
may be enough to control the sequelae of ulceration. If such
treatment fails, then PDL treatment should be considered.
Using lower fl uences (5-7 J/cm
2
) with cryogen cooling, this
laser emits a wavelength of light that is readily and specifi cally
absorbed by the chromophore oxy-HgB; superfi cial vessel clo-
sure is induced such that further ulceration may be minimized,
involution is promoted, and pain is subjectively decreased
within 2 to 3 days after a single treatment (156). Optimal fre-
quency of treatments remains controversial; one review of
PDL therapy for treatment of ulcerated hemangiomas found
that the majority of patients responded to laser therapy alone
with a mean number of two treatments performed in a sequen-
tial pattern at three- to four-week intervals (157). Traditional
treatment endpoints include cutaneous healing and reepithe-
lialization of the wound or involution of the hemangioma.
Management of IH, from about 1930 to 1950, consisted
primarily of preemptive surgical excision and X-irradiation
therapy. In the mid-1960s, systemic corticosteroids, with
their side effect profi le that includes growth retardation,
increased susceptibility to infectious disease, irritability, and
hypertension, were found to be an effective treatment for
those lesions severe enough to require systemic therapy
(e.g., those causing amblyopia or breathing diffi culty or
those threatening permanent functional or cosmetic defor-
mity). In 1991, Ezekowitz et al. published on the novel use of
interferon-alpha (IFN-alpha) as a systemic therapy in
patients with life-threatening IH who had failed systemic
corticosteroids (158). By the late 1990s, however, spastic
diplegia and other serious side effects were recognized that
severely limited the use of IFN therapy (159). The use of
topical imiquimod 5% cream, more common in Asia, has
been anecdotally effi cacious, but well-controlled trials are
lacking (160). Contact cryotherapy, more commonly utilized
in Europe, has also been used to treat small hemangioma
(161) Surgical intervention has traditionally been reserved
for the subset of cases in which potentially cosmetically or
functionally deforming lesions do not respond to medical
therapy or when bleeding or ulceration has occurred. Exci-
sion has also proved to be helpful for defi nitively managing
residual fi brofatty tissue left behind by involuted hemangio-
mas. Arterial embolization has been used to reduce tumor
volume and fl ow in rare cases when life-threatening IH cause
high output cardiac failure.
These aforementioned management strategies have
been rendered all-but-second line when, in June 2008, Leaute-
Labreze et al. reported the serendipitous observation that sys-
temic treatment with the nonselective beta-blocker propranolol
appeared an effective treatment for IHs (162). Clinical
results using this medication may be noticed in as little as
24-48 hours. The proposed therapeutic effects of propranolol
are direct vasoconstriction; apoptosis of capillary endothelial
cells; and decreased expression of vascular endothelial growth
factor and basic fi broblast growth factor genes through down-
regulation of the RAF/mitogen-activated protein kinase path-
way (163). Optimal dosage and frequency of oral propranolol
administration are still being investigated but appear to be in
the range of 1-3 mg/kg/day, divided BID or TID with meals.
Reported side effects include hypoglycemia and hypotension,
with multicenter trials actively attempting to gauge the true
incidence of these rare but potentially serious complications.
Other beta-blocker therapies, such as topical timolol maleate
0.5% gel, have yielded similar positive results, especially for
smaller, more superfi cial hemangiomas (164).
The PDL, commercially available since 1988, adds a direct
intervention to the treatment arsenal for IH, especially for
ulcerated lesions. The use of PDL therapy to help slow prolif-
eration of and promote involution of otherwise uncomplicated
hemangiomas, however, remains controversial. Evidence-based
analysis of lasers for IH reveals that the specifi c laser utilized
and specifi c settings are often not specifi ed in published studies.
Likewise, the natural history of the lesion itself makes it diffi cult
to sort out if the laser is simply speeding up what would occur
naturally with time. Additionally, optimal timing and frequency
of treatments vary greatly among laser surgeons. Limitations of
laser surgery for IH include focal scarring, diffuse ulceration,
pain, fi nancial cost, and a questionable impact on “deep”
lesions.
In 1992, Garden et al. demonstrated prospectively that early
PDL therapy, performed when the lesions are relatively fl at, can
help reduce the proliferative growth phase with minimal adverse
events (165). This work was supported by subsequent studies
by Barlow et al. (166), and Hohenleutner and Landthaler (167).
A 1-year analysis study by Batta et al. showed mixed results
(168). In this randomized controlled study of early PDL-
treatment versus observation only for uncomplicated IH, the
authors failed to demonstrate a signifi cant difference in the
number of children with minimal residual signs or complete
clearance or whose parents considered the hemangioma to be a
problem at 1 year. Additionally, PDL-treated infants were noted
to have a signifi cantly higher rate of skin atrophy and hypopig-
mentation. On the other hand, 30% of laser-treated patients
versus 7% in the observation-only group were “completely
