Pediatric Dermatology Vol. 27 No.

2 195–196, 2010

Severe Hypoglycemia During Successful

Treatment of Diffuse Hemangiomatosis with
Propranolol
Ernesto Bonifazi, M.D.,* Angelo Acquafredda, M.D.,  Antonella Milano, M.D.,*
Osvaldo Montagna, M.D.,à and Nicola Laforgia, M.D.à
*Pediatric Dermatology Unit, University of Bari, Bari, Italy,  Department of Pediatrics Trambusti, Policlinico
Bari, Bari, Italy, àDepartment of Neonatology, Policlinico Bari, Bari, Italy

Abstract: A 27-day-old male infant with diffuse hemangiomatosis of the

skin and liver was treated with oral propranolol at a dosage of 2 mg ⁄ kg per
day. Five months later skin and liver hemangiomas regressed almost com-
pletely. After 160 days of onset of propranolol, the patient presented with
seizures on waking up. Laboratory examinations showed blood glucose of
15 mmol (n.v. 50–110) and increased ketone bodies. Propranolol was re-
commenced at a lower dosage the day after the crisis and then withdrawn
when the baby was aged ten months. Hypoglycemia is the most frequent and
insidious side effect of propranolol, mainly occurring in circumstances with
diminished oral intake. Although the risk appears small, increased vigilance
for hypoglycemia in children on chronic propranolol treatment who have
decreased caloric intake for any reason seems prudent.

Diffuse hemangiomatosis is characterized by multiple
skin hemangiomas associated with visceral, mainly liver
hemangiomas (1). The first choice for therapy of the
most severe hemangiomas is corticosteroids which,
although usually effective, are associated with significant
side effects. Recently, some authors (2) proposed oral
propranolol as an alternative treatment. Propranolol is
effective in skin hemangiomas (3), and also in liver
hemangiomas, although its use is not devoid of side
effects, as the case of diffuse hemangiomatosis here
reported showed.
An infant presented at age 20 days with around 80
skin hemangiomas, the largest on the right forearm and
breast (Fig. 1A). MRI showed multiple solid tumors in
the liver suggestive of hemangiomas (Fig. 1C). Due to
the development of new cutaneous hemangiomas and
increases in the earlier cutaneous and liver hemangiomas,
at 27 days of age oral propranolol was started at a dosage
of 2 mg/kg per day in 3 divided doses. Initially, heart rate,
arterial pressure and glucose levels did not show signifi-
cant changes. Five months later, minimal residual spots
replaced the largest hemangiomas (Fig. 1B). Also, liver
hemangiomas regressed almost completely (Fig. 1D).
After 160 days of onset of propranolol, the patient
presented with irritability and seizures on waking up.
Laboratory examinations showed blood glucose of
15 mmol ⁄ L (n.v. 50–110) and increased ketone bodies.
The previous night, the patient had taken his last feed at

Address correspondence to Prof. Ernesto Bonifazi, M.D.,

Pediatric Dermatology Unit, University of Bari, P.za G. Cesare,
11, Policlinico, 70124 Bari, Italy, or e-mail: ejpd@dermatologia-
pediatrica.com

DOI: 10.1111/j.1525-1470.2009.01081.x

 2010 Wiley Periodicals, Inc. 195

196 Pediatric Dermatology Vol. 27 No. 2 March ⁄ April 2010
A B
C D
Figure 1. Diffuse hemangiomatosis. Skin (panel A) and liver (panel C) hemangiomas at the age of 21 days, before starting
propranolol 2 mg ⁄ kg ⁄ day. Residua of skin (panel B, arrows) and liver (panel D) hemangiomas at the age of 6 months, 5 months
after the onset of propranolol.
11 P.M., propranolol at 3 A.M. and had not woken up
as usual at 6 A.M. for his first feed. In the subsequent
days, glucose monitoring, physical examination, and
other laboratory examinations were within normal
limits. The neuropsychiatry examination ruled out
pathological sequelae.
Propranolol 0.3 mg ⁄ kg was recommenced the day
after the crisis and then progressively increased up to
1.5 mg ⁄ kg ⁄ day. Beginning in the ninth month, pro-
pranolol was tapered and then withdrawn within
1 month. Physical and ultrasonography findings
persisted unchanged in the following 2 months.
Propranolol is a non-selective beta-blocker released in
1964 (4). Historically, it is rarely used in the first months.
However, its use in this age group could become more
frequent with its use in the treatment of severe heman-
giomas. Among beta-blockers, propranolol is more fre-
quently associated with side effects, although no cases of
death have been so far reported in the first 6 years (4).
Hypoglycemia is the most frequent and insidious side
effect, mainly occurring in circumstances with dimin-
ished oral intake (4). Preoperative and nighttime (5)
fasting can increase risks of propranolol-induced hypo-
glycemia. The correction of hypoglycemia involves low-
ering of insulin, which is the only glucose lowering factor,
and numerous glucose-elevating factors. Among the
latter, in hierarchical arrangement, in the first place there
is glucagon, catecholamines, growth hormone, and cor-
tisol. Propranolol inhibits lowering of insulin, glucagon
responses to hypoglycemia, and hepatic and muscle
glycogenolysis (6). On the other hand, propranolol in-
creases secretion of growth hormone in response to
hypoglycemia (6).
In the case here reported, the nighttime intake of
propranolol and the prolonged fasting favored hypo-
glycemia, suggesting that propranolol should be given
during the daytime and followed by feeding within a
short time. Although the risk appears small, increased
vigilance for hypoglycemia in children on chronic pro-
pranolol treatment who have decreased caloric intake for
any reason seems prudent.
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