DOI: 10.1111/pde.

13372

Pediatric
Dermatology

Topical 1% propranolol ointment with occlusion in treatment

of pyogenic granulomas: An open-label study in 22 children

Iria Neri MD | Carlotta Baraldi MD | Riccardo Balestri MD | Bianca Maria

Piraccini MD | Annalisa Patrizi MD

Section of Dermatology, Department of

Experimental, Diagnostic and Specialty
Medicine, Saint Orsola-Malpighi Hospital,
University of Bologna, Bologna, Italy
Correspondence
Carlotta Baraldi, MD, Section of
Dermatology, Department of Experimental,
Diagnostic and Specialty Medicine, Saint
Orsola-Malpighi Hospital, University of
Bologna, Bologna, Italy.
Email: carlotta.baraldi@gmail.com
Abstract
Background: Pyogenic granuloma (PG) is a common, acquired, benign vascular neo-
plasm of the skin and mucous membranes. It occurs most often in children and ado-
lescents. First-line treatment options for PG are based on destructive approaches.
Pain, permanent scarring, and pigmentation are potential complications of these
therapies.
Methods: This single-arm, open-label, prospective study evaluated the efficacy of
topical propranolol for treatment of PGs in children. All patients clinically diagnosed
with cutaneous PG consecutively at the Dermatology Pediatric Outpatient Service
of the University of Bologna from January 2010 to December 2010 received a com-
pounded formulation of propranolol ointment 1%.
Results: We found propranolol ointment to be effective in consecutive patients;
59.0% completely regressed in a mean of 66 days, 18.2% remained stable, and
22.7% did not respond. No side effects (eg, skin irritation, allergy, bleeding) were
observed.
Conclusion: Topical propranolol ointment 1% with occlusion appears to be an effec-
tive treatment for PGs in children. Early treatment was associated with a more
favorable outcome.

KEYWORDS
neoplasms, benign, therapy, topical

1 | INTRODUCTION requiring sedation. Another potential complication of surgical

removal is recurrence or development of multiple PGs in the treated
Pyogenic granuloma (PG), also known as lobular capillary heman- area.2
gioma, is a common, acquired, benign vascular neoplasm of the skin Nonsurgical treatments (eg, imiquimod, silver nitrate) have been
and mucous membranes. It occurs most often in children and adoles- attempted, with variable results.3 Recently Lee and colleagues4 trea-
cents but also can be observed in adults, particularly pregnant ted six patients with PG with timolol, a topical beta-blocker, and
women.1 Malik and Khorsand5 have used timolol 0.5% ophthalmic gel to treat
First-line treatment options for PG include destructive two PG cases. All patients in these reports showed at least partial
approaches such as cryosurgery, cautery with electrodesiccation, sur- response.
gical excision, and laser therapy. Pain, permanent scarring, and pig- We present a single-arm, open-label, prospective study whose
mentation are potential complications of these therapies. Moreover, objective was to evaluate the efficacy of a new ointment-based
in young children, surgical procedures may be difficult, often formulation of propranolol for the treatment of PGs.

Pediatric Dermatology. 2018;35:117–120. wileyonlinelibrary.com/journal/pde © 2017 Wiley Periodicals, Inc. | 117

118 | Pediatric NERI ET AL.

Dermatology
T A B L E 1 Patient characteristics posttreatment photographs and size as the primary outcome.
Characteristic Value Improvement was defined as no improvement, mild improvement
or no additional improvement after initial partial response, and
Age, mean (range) 7 y (2 mo to 15 y)
complete resolution of PG. The treatment was considered ineffec-
Sex, n (%)
tive and stopped if no improvement was observed after the first
Male 10 (45.5)
6 weeks of treatment.
Female 12 (54.5)
In the other cases, treatment was discontinued after complete
Race, n
resolution of PG, no improvement in three consecutive evaluations,
Caucasian 21
or a maximum of 5 months of therapy without complete regression
Hispanic 1 of PG. In all patients showing no response or partial response, PGs
Lesion size, cm, mean (range) 0.42 (0.2-0.8) were surgically treated.
Lesion duration, days, m (range) 66 (14-150) The local ethics committee of the University of Bologna Institute
Location, n (%) approved the study and written informed consent was obtained
Chest and back 13 (59.1) from both parents.
Face 6 (27.3)
Upper extremities 2 (9.1)
3 | RESULTS
Scalp 1 (4.5)

Twenty-two children were enrolled in the study (10 male, 12 female)

2 | MATERIAL AND METHODS
All patients with a clinical diagnosis of cutaneous PG seen at the
Dermatology Pediatric Outpatient Service of the University of
Bologna from January 2010 to December 2010 were recruited and
followed for 2 years.
Inclusion criteria were age 4 weeks and older and PG diameter
between 0.1 and 1 cm. Exclusion criteria were propranolol hypersen-
sitivity in the patient or a first-degree relative and cardiovascular dis-
ease that contraindicated inclusion in the study.
Each patient received propranolol ointment 1% (oral propranolol
crushed pills/petroleum jelly: 10 mg/1 g, compounded by our che-
mist). Parents were instructed to apply this product on the PG twice
daily under a thin, flexible, 2 cm2, hydrocolloid occlusive dressing
(Comfeel Plus Transparent, Coloplast, Bologna, Italy). Follow-up visits
were scheduled every 2 weeks.
At each visit, the primary investigator (NI) estimated the per-
centage of clinical improvement of the PG using pre- and
with a median age of 7 years (range 1-15 years). Thirteen PG were
exophytic and the remaining nine were pedunculated. The main
characteristics of the patients and PGs are reported in Table 1. Topi-
cal propranolol ointment was used for 14-150 days (median
82 days).
The PG regressed completely in 13 patients (59%) in a mean
time of 66 days (range 14-150 days) (Figure 1). In four patients, the
PG improved initially and then remained stable (18%) (Figure 2), and
in five (23%) they did not change (Table 2). These latter nine cases
were treated with surgical removal, and histology confirmed the clin-
ical diagnosis of PG in all. At follow-up, 2 years after regression,
there was no scarring or relapse in the 13 PGs cured using 1%
propranolol ointment.
No irritation, allergy, bleeding, or other topical complications
were observed during treatment. Response to treatment was rapid
and parents commented that they could see improvement even in
the first 2 weeks of treatment. In two bleeding PGs, bleeding
stopped rapidly after initiation of treatment.

(A) (B) (C)

F I G U R E 1 Patient with complete regression of pyogenic granuloma after treatment with topical propranolol: (A) first visit; (B) first control;
(C) completed regression
NERI ET AL. Pediatric | 119
Dermatology

(A) (B)

F I G U R E 2 Patient with partial

regression of pyogenic granuloma after
treatment with topical 1% propranolol: (A)
first visit; (B) partial regression

T A B L E 2 Outcome of PGs after treatment with 1% topical propranolol ointment under occlusive dressing
Change Age, y Sex Location Type of PG Dimension, cm Bleeding
No improvement after 6 wk 14 Female Chest Pedunculated 0.4 No
2 Male Back Exophytic 0.6 No
11 Male Chest Pedunculated 0.5 No
5 Male Lip Exophytic 0.3 No
1 Male Cheek Exophytic 0.3 Stopped after 2 wk
Partial regression
Stopped improving after 2 wk 15 Female Back Pedunculated 0.8 No
Stopped improving after 8 wk 5 Female Forehead Exophytic 0.4 No
Stopped improving after 12 wk 15 Female Back Pedunculated 0.6 No
Stopped improving after 16 wk 10 Female Chest Exophytic 0.5 No
Complete regression
In 11 d 3 Male Arm Exophytic 0.4 No
In 2 wk 9 Male Chest Pedunculated 0.5 No
In 4 wk 7 Male Back Exophytic 0.5 No
9 Female Scalp Exophytic 0.2 No
4 Male Arm Exophytic 0.4 No
2 Female Chest Exophytic 0.3 No
2 mo Female Navel Pedunculated 0.8 No
In 12 wk 1 Male Nose Exophytic 0.3 No
1 Male Chest Exophytic 0.3 No
4 Female Back Exophytic 0.3 No
In 14 wk 2 Male Forehead Exophytic 0.3 Stopped after 2 wk
In 16 wk 15 Female Chest Pedunculated 0.4 No
In 20 wk 10 Female Forehead Exophytic 0.2 No

4 | DISCUSSION have reported the use of topical beta-blockers in uncomplicated,

mainly small superficial IHs.8–13
Oral propranolol, a nonselective beta-adrenergic receptor blocker, Recently PGs have been treated with topical beta-blockers
has become first-line systemic treatment for complicated infantile with good results. Complete resolution of a single PG was seen in
hemangiomas (IHs), even those that are ulcerated.6,7 Several articles three cases using 0.5% timolol gel applied twice a day: a 5-
120 | Pediatric
Dermatology
month-old girl with a PG on the cheek treated for 1 month,14 a
14-year-old with a PG on a finger that was fully cured after
3 weeks,4 and a 2-year-old boy with a PG on the scalp.15 Cases
series of PG treated with topical timolol have been reported in
the literature.3,16 Wine Lee and colleagues reported a case series
of six children with PG treated with topical timolol gel in different
concentrations (0.5% in three cases, 2% in three cases) two or
three times per day, with complete or partial resolution in
2 months.4 Gupta and colleagues16 reported a series of 10
patients (ages 15-50 years) with PG treated with 0.5% timolol
four times a day. Five had completed response, two had partial
response, and two had no response. Oke and colleagues17 used
0.5% timolol gel twice daily to treat periocular PG in four chil-
dren, all of whom had complete resolution with no recurrence for
at least 3 months. Treatment improved bleeding, when present, in
all patients.14 Finally, a recalcitrant case of chronic PG on the
scalp of a healthy boy showed complete resolution and healing
after application of topical timolol.18
Surgical excision of PG has the advantage of allowing for
histologic confirmation of the diagnosis of PG but, depending on the
size and location, may be difficult in certain children and infants,
necessitating sedation or general anesthesia to perform surgery.
Moreover, PG can recur after excision, and surgical removal results
in a scar, which may be an important treatment consideration.
These issues highlight the potential advantages of topical ther-
apy.3,19 The majority of our 22 patients treated with topical 1% pro-
pranolol ointment responded, and none of the regressed PG
relapsed within 2 years of follow-up.
Topical 1% propranolol ointment can be effective in treating PG
in children and the hydrocolloid dressing may increase the penetra-
tion and efficacy of the treatment. This therapy was more effective
in small, exophytic PG and we did not note any differences between
the different affected anatomic sites. No topical or systemic adverse
reactions were noted.
Limitations of our study include the small number of cases and
the absence of a placebo control group.
5 | CONCLUSION
Given the good tolerance of the topical medication in the cases trea-
ted and the apparent absence of side effects, we believe that the
topical use of beta-blockers including propranolol is an important
addition to the treatment armamentarium for PGs, particularly those
in exposed areas. Placebo-controlled studies should be conducted to
further evaluate and confirm these findings.
ORCID
Carlotta Baraldi http://orcid.org/0000-0002-3115-9407
Riccardo Balestri http://orcid.org/0000-0002-0885-054X
NERI ET AL.
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How to cite this article: Neri I, Baraldi C, Balestri R, Piraccini
BM, Patrizi A. Topical 1% propranolol ointment with
occlusion in treatment of pyogenic granulomas: An open-label
study in 22 children. Pediatr Dermatol. 2018;35:117–120.
https://doi.org/10.1111/pde.13372