Current management of complicated infantile hemangiomas: Atenolol or Propranolol?

IBEROAMERICAN JOURNAL OF MEDICINE 03 (2022) 133-135

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Editorial

Current management of complicated infantile hemangiomas:
Atenolol or Propranolol?

Ivan David Lozada-Martinez %°:*\, Claudia Marcela Castafieda-Moreno ©‘, Juan Pablo
Duran-Tabera 4“, Gloria Patricia Crecian-Pérez °

° Medical and Surgical Research Center, Future Surgeons Chapter, Colombian Surgery Association, Bogota, Colombia

> Grupo Prometheus y Biomedicina Aplicada a las Ciencias Clinicas, School of Medicine, Universidad de Cartagena, Cartagena, Colombia
‘Department of Medicine, Universidad Cooperativa de Colombia, Villavicencio, Colombia

4 Department of Medicine, Universidad del Quindio, Armenia, Colombia

© Department of Medicine, Universidad Libre, Barranquilla, Colombia

ARTICLE INFO

Article history: Keywords:

Received 04 June 2022 Hemangioma Adolescent

Received in revised form 28 June 2022 Infant Adrenergic Beta-
Accepted 01 July 2022 Child antagonists

© 2022 The Authors. Published by Iberoamerican Journal of Medicine. This is an open access article under the CC BY license
(http://creativecommons.org/licenses/by/4.0/).

Manejo actual de los hemangiomas infantiles complicados: ;Atenolol o Propranolol?

INFO. ARTICULO

Historia del articulo: Palabras clave:

Recibido 04 Junio 2022 Hemangioma Adolescente

Recibido en forma revisada 28 Junio 2022 Infante Antagonista Beta-
Aceptado 01 Julio 2022 Nifio adrenérgico

© 2022 Los Autores. Publicado por Iberoamerican Journal of Medicine. Este es un articulo en acceso abierto bajo licencia CC BY
(http://creativecommons. org/licenses/by/4.0/).

HOW TO CITE THIS ARTICLE: Lozada-Martinez ID, Castafieda-Moreno CM, Duran-Tabera P, Crecian-Pérez GP. Current
management of complicated infantile hemangiomas: Atenolol or Propranolol? Iberoam J Med. 2022;4(3):133-135. doi:
10.53986/ibjm.2022.0025.

* Corresponding author.
E-mail address: ilozadam @unicartagena.edu.co
ISSN: 2695-5075 / © 2022 The Authors. Published by Iberoamerican Journal of Medicine. This is an open access article under the CC BY license
(http://creativecommons. org/licenses/by/4.0/).
https://doi.org/10.53986/ibjm.2022.0025

134 IBEROAMERICAN JOURNAL OF MEDICINE 03 (2022) 133-135

Infantile hemangiomas are the most common vascular tumor
in childhood, occurring in more than 10% of infants in their
first year of life [1, 2]. The vast majority appear weeks after
birth as telangiectatic patches, which grow rapidly and
diffusely until before the age of 6 months, until they become
reddish, delimited, dome-shaped protuberances in deep
areas [3]. They are mainly located on the face and neck.
From the age of one year, these lesions grow parallel to the
child's development. The regression of the lesions is almost
100% at 10 years of life [1]. However, depending on the
evolution and expansion of the lesions, they can become
complicated and bleed uncontrollably, ulcerate and cause
pain, disfigure the face, hinder activities of daily living,
compromise the child's functional ability and substantially
influence mental health [2]. This is not to mention that
hemangiomas are associated with certain syndromes such as
the PHACES (Posterior
malformations/Hemangiomas/Arterial anomalies/Cardiac
defects/Eye abnormalities/Sternal — cleft/Supraumbilical
raphe syndrome) or PELVIS/SACRAL/LUMBAR (Perineal
hemangioma/External genitalia
malformations/Lipomyelomeningocele/Vesicorenal
abnormalities/Imperforate anus/Skin tag), which hinder the
management and make the recovery process less tolerable
[1-4].

For these complicated hemangiomas, the use of beta-
blockers has been described as effective, but not entirely
safe. [3-6]. Atenolol and propranolol have been two agents
frequently studied in the last decade in the control of this
condition, and although no significant differences have been
found between the two, there is much discussion at present
about which drug to use [4-6]. Propranolol is a non-selective
beta-blocker, which has been associated with several

fossa

adverse effects, mainly in those with respiratory system
disorders [4, 6]. Atenolol is a cardioselective beta-blocker,
which can significantly affect patients with abnormalities of
the cardiovascular system (mainly those with PHACES
syndrome, who are at increased risk of heart defects) [4, 6].
Therefore, there is a need to study in depth and be very
critical in the therapeutic plan of those patients with
complicated infantile hemangiomas.

Abarztia-Araya et al [4] published in 2014 one of the first
and most representative clinical trials to compare Atenolol
and Propranolol in uncomplicated infantile hemangiomas.
Although the authors found that Propranolol was more
effective than Atenolol in terms of complete response
(lesion resolution over time: 60% vs. 53.8%), these results
were not significant (p= 0.68). However, a very strong
limitation was the study sample, only 23 patients [4].
Therefore, up to that date, the problem question remained

unresolved. Recently, in 2021, a trial was published with a
more representative sample (337 participants), where
Propranolol vs Atenolol was evaluated in the management
of complicated infantile hemangiomas,
outcome was the response or non-response at 6 months [6].

whose main

The average age of the patients was 10 weeks and more than
70% were women. After 6 months, Propranolol and
Atenolol response were 93.7% and 92.5%, respectively. The
hemangioma activity score was similar at 1 week and 4
weeks after treatment (OR 1.03; 95% CI, 0.886 - 1.206) [6].
Although there were no significant differences in quality of
life, ulcer healing time or rebound rate, the presence of
adverse events was more frequent in the Propranolol group
(70.0% vs. 44.4%). The complete response rate was similar
at 24 months (82.1% vs 79.7%) [6]. Thus, it was concluded
that Atenolol has an equally effective response as
Propranolol, but is safer.

Only one month after the aforementioned trial was
published, Mufioz-Garza et al [5], who evaluated the impact
of Timolol vs. placebo in the early proliferative phase of
uncomplicated infantile hemangioma, published another
Spanish trial. Although there were only 69 patients, with an
average age of 48 days, there was no evidence of superiority
compared to placebo with respect to complete resolution at
24 weeks (42% vs. 36%, p= 0.37), nor to variation in tumor
size. The only favorable finding was an improvement in
color and the absence of systemic adverse effects [5]. The
most recent systematic review that has studied the effects of
certain interventions in the management of infantile
hemangiomas (laser, beta-blockers, radiation therapy and
steroids) was done by Novoa et al [3] and published in 2018.
The authors included 28 containing 1,728
participants, from various countries and ranging in age from
12 weeks to 13 years of age. Among the outcomes evaluated,
the favorable result of propranolol vs. placebo on tumor
volume reduction (RR 16.61; 95% CI, 4.22 - 65.34) and
clearance (45.9%; 95% CI, 11.60 - 80.20) was highlighted
[3]. No serious short- or long-term adverse effects were
evident (RR 1.05; 95% CI, 0.33 - 3.39). However, the latter
finding was not significant, and had a low level of quality.
The use of topical Timolol (0.5% gel) vs. placebo showed a
reduction in redness (RR 8.11; 95% CI, 1.09 - 60.09), with
no adverse events reported [3]. When comparing topical
Timolol vs. oral Propranolol with respect to the impact on

studies

tumor size, no significant differences were observed (RR
1.13; 95% CI, 0.64 - 1.97). However, effects that are more
adverse were reported in the Propranolol group [3]. It should
be noted that the authors reported that the quality of the
outcomes evaluated and of the studies was moderate to low,
the heterogeneity of the population studied was high (the age

IBEROAMERICAN JOURNAL OF MEDICINE 03 (2022) 133-135 135

range was very wide), and the available studies that have
evaluated efficacy and safety between drugs are almost
nonexistent [3].

At present, there are no clinical trials from Latin America or
from low- and middle-income countries of similar regions.
In order to comply with global health objectives [7], which
establish the search for entities that affect early childhood
and the control of the burden of pediatric diseases. It is
necessary to encourage the design and systematization of
data regarding the approach and outcome of infants and
adolescents with complicated infantile hemangioma, to
facilitate the resolution and ensure that there are no sequelae
of any kind [8]. In addition, due to current barriers in low-
and middle-income countries, such as timely access to
specialize health care, it is imperative to design policies or
groups that can reach hard-to-reach areas to identify or rule
out these types of tumors, if they are mistaken for other
[8, 9]. Genomic
characterize the behaviour of these tumors in regions where
complicated infantile hemangiomas have not been studied in
depth, to identify new therapeutic targets for a context-
specific stratification of each population, according to their

conditions studies are needed to

needs [9, 10]. These tumors, because they resolve at
approximately 10 years of age in the vast majority of cases
[1, 2], can entail a high catastrophic expense for a very long
period of time, which can affect the development of the child
and the functionality of his family.

To date, there is no sufficiently effective, efficient and safe
therapeutic agent that is superior to other therapeutic tools
designed for the management of complicated infantile
hemangiomas. Although Propranolol has been shown to be
superior to Atenolol in terms of efficacy, itis associated with
numerous adverse events. Atenolol has been shown to be
similar to Propranolol and other agents such as Timolol,
with an acceptable safety profile. However, the current
evidence is heterogeneous and of low quality. In this order
of ideas, the therapeutic plan for complicated infantile
hemangiomas should be multidisciplinary and personalized.

1. CONFLICT OF INTERESTS

The authors have no conflict of interest to declare. The
authors declared that this study has received no financial
support.

2. REFERENCES

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10.12788/j.sder.2016.050.¢

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