Master case presentation

Journal of Cosmetic Dermatology, 14, 161--166

Intralesional botulinum toxin type A equally effective and better

tolerated than intralesional steroid in the treatment of keloids: a
randomized controlled trial
Eman Shaarawy, MD, Rehab A. Hegazy, MD, & Rania M. Abdel Hay, MD
Dermatology department, Faculty of Medicine, Cairo University, Cairo, Egypt

Summary

Intralesional (IL) corticosteroid therapy is a treatment for keloids. IL botulinum toxin

type A (BTA) has been postulated in such an indication with controversial reports.
To compare efficacy and safety of IL BTA to the IL corticosteroid therapy in
treatment of keloids. Twenty-four patients with keloids were randomly divided into
two equal groups: receiving IL steroid repeated every 4 weeks for six sessions (group
A) and IL BTA 5 IU/cm3 repeated every 8 weeks for three sessions (group B).
Objective parameters (hardness, elevation, and redness), subjective complaints
(itching, pain, and tenderness), patient satisfaction, and side effects were evaluated.
There was a significant decrease in the volume of the lesions after treatment
(P < 0.01), with a volume reduction of 82.7% and 79.2%, respectively, in both
groups. A significant softening of lesions vs. baseline was observed (P < 0.01), with
statistically significant improvement in softening in group A (P < 0.01). There was a
significant decrease in height of lesions and in redness score compared with baseline
(P < 0.01) with no significant difference in between both groups. All patients
mentioned a significant reduction of their subjective complaints (P < 0.01) that were
more significant in group B. Skin atrophy and telangiectasia were evident in three
patients of group A. The efficacy and safety of the IL BTA were clearly evident in the
current work from the rapid significant amelioration of the subjective complaints and
the comparable significant improvement of the objective parameters as well as the
volume of the keloids in comparison with the IL corticosteroids.
Keywords: botulinum toxin, intralesional steroids, off-label indication, scar

Introduction
Keloidal scarring is one of the frustrating clinical problems1 that can be associated with severe clinical symptoms.2 Keloid formation has been ascribed to altered
growth factor regulation, aberrant collagen turnover,
genetics, immune dysfunction, sebum reaction, and
altered mechanics.3
Correspondence: Rania Abdel Hay, MD, 13th Abrag Othman, Kournish el
Maadi, 11431 Cairo, Egypt. E-mail: raniamounir@kasralainy.edu.eg
Accepted for publication July 1, 2014

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Most therapeutic approaches remain unsatisfactory,

and no ideal therapy exists for keloids.4 The search for
alternative efficacious therapeutic options with a high
safety profile seems to be prudent.5 Nevertheless, intralesional (IL) corticosteroid therapy with triamcinolone acetonide is regarded by many to be the first line
of therapy in the treatment of keloids.4
In the early 1980s, botulinum toxin type A (BTA)
was first introduced for medical indications such
as strabismus and blepharospasm.6,7 Consequently,
its cosmetic use in treating wrinkles has become
widespread.8,9 Many off-label cosmetic applications

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IL BTX in keloids

. E Shaarawy et al.

of BTA are under evaluation, 10 and the efficacy of

IL BTA in the treatment of keloids has been postulated. 1015
Aiming to compare the efficacy and safety of IL BTA
in the treatment of keloids to the well-documented IL
corticosteroid therapy, this study was designed.

Methods
This randomized double-blinded comparative study has
been approved by our dermatology research ethical
committee, Faculty of Medicine, Cairo University.
It included 24 female patients with post-traumatic or
idiopathic keloids. Patients were recruited from Cairo
University Hospital Outpatient Clinics. The diagnosis of
keloids was confirmed by three dermatologists based
on the progressive nature of the scarring tissue and
the invasion of the surrounding normal skin.
Patients were randomly divided into two groups.
Group A (12 patients) received IL steroid injection (Triamcinolone, Kenacort 1:2 saline i.e., 10 mg/cc),
repeated every 4 weeks for six sessions/or complete
improvement of the keloid. Group B (12 patients)
received IL BTA injection 5 IU/cm3, repeated every
8 weeks for three sessions/or complete improvement of
the keloid. The total duration of the treatment plan
was 6 months. Randomization was carried out using
computer-generated random sequence prepared by the
statistician, and the sequence was kept in the pharmacy.
Clinical assessment

At each visit, clinical assessment was carried out by

two unchanged blinded dermatologists. The assessment included documenting objective parameters
(hardness, elevation, and redness) and subjective complaints (itching, pain, and tenderness) on a scale of 0
(none) to 3 (maximum),16 with the score 0 revealing
minimum complaint and score 3 revealing maximum
complaint. Furthermore, evaluation of the volume of
the keloids was carried out to calculate the dosage,
using Alginoplast (alginate; Heraeus-Kulzer Company, Hanau, Germany) and saline.17 Patient satisfaction has also been evaluated as unsatisfied, satisfied,
and highly satisfied, and any side effects were
reported. Photographs were taken before treatment
and at 7 months (end of treatment) after the start of
our treatment protocol.
Statistical analysis was carried out for the results
before treatment and at 7 months (end of treatment)
after the start of our treatment protocol.

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Statistical analysis

Data were coded and entered using the statistical package for social science (SPSS) version 19 (SPSS Inc.,
Chicago, IL, USA). Data were summarized using
mean  SD for quantitative variables and % for qualitative variables. Comparisons between groups were
carried out using Students t-test. P < 0.05 was considered statistically significant.

Results
This study included 24 female patients with age ranged from 10 to 53 years (mean  SD 29.29 
11.793). The duration of their keloids ranged from 0.5
to 6 years (mean  SD 2.8  1.474). Group A
included 12 patients with mean age 32.42 
13.242 years and mean disease duration 2.79 
1.453 yearsfive (41.7%) of them had skin phototype
(SPT) III, and seven (58.3%) had SPT IVwhile group
B included 12 patients with mean age 26.17 
9.703 years and mean disease duration 2.82 
1.559 yearsfour (33.3%) of them had SPT III, and
eight (66.7%) had SPT IV. There was a nonsignificant
difference between both groups regarding the age,
disease duration, SPT, and the volume of keloids at
baseline (P = 0.201, 0.957, 0.673, and 0.940, respectively).
There was a significant decrease in the volume of
the lesions in all patients 7 months after treatment
compared with baseline (P < 0.01), with a volume
reduction of 82.7% (Figs 1 and 2) and 79.2% (Figs 3
and 4), respectively, in both groups. There was a
nonsignificant difference in both groups regarding the
clinical assessment after treatment (Table 1).
A significant softening of lesions vs. baseline was
observed in all patients at the follow-up visits after the
7th month (P < 0.01), with statistically significant
improvement in softening in group A (P < 0.01).
There was a significant decrease in height of lesions
and in redness score in the 7th month in all patients
compared with baseline (P < 0.01) with no significant
difference in between both groups. All patients mentioned a significant reduction of their subjective complaints starting 2 months after the treatment
(P < 0.01); however, these subjective symptoms
improved more significantly in group B (Table 1).
Six (50%) of patients in group A were highly satisfied, five (42%) of them were satisfied, and only one
(8%) was unsatisfied with their results, while nine
(75%) of patients in group B were highly satisfied, and
three (25%) of them were satisfied with their results.

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IL BTX in keloids

. E Shaarawy et al.

Figure 1 A female patient (Group A) with a keloid at her left ear

before treatment.
Figure 3 A female patient (Group B) with a keloid at her chest
before treatment.

Figure 2 The same patient (Group A) with almost complete cure

7 months after IL steroid treatment.

The IL treatment in both groups was generally well

tolerated by all patients. Mild pain or discomfort, during and few hours after the procedure, was reported.
Infection was not reported. Skin atrophy and telangiectasia were evident in three patients (25%) of those
receiving the IL steroid during the follow-up period.

Discussion
The current RCT comparing the efficacy and safety
of IL BTA to the well-documented IL steroids in the

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Figure 4 The same patient (Group B) with moderate improvement 7 months after IL BTX treatment.

treatment of keloids offers further proof to the eligibility

of this rather newly postulated indication for this
rather old material. The value of using IL BTA in the
treatment of keloids was clearly evident through the
rapid significant amelioration of the subjective complaints and the comparable significant improvement of

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IL BTX in keloids

. E Shaarawy et al.

Table 1 Clinical assessment of all patients before and 7 months after treatment

Volume/cm3 (Range, mean  SD)

Before treatment
7 months after treatment
P-value
% volume reduction
Hardness (Score 03) (Range, mean  SD)
Before
7 months after treatment
P-value
Height (Score 03) (Range, mean  SD)
Before treatment
7 months after treatment
P-value
Redness (Score 03) (Range, mean  SD)
Before treatment
7 months after treatment
P-value
Itching (Score 03) (Range, mean  SD)
Before treatment
7 months after treatment
P-value
Pain (Score 03) (Range, mean  SD)
Before treatment
7 months after treatment
P-value
Tenderness (Score 03) (Range, mean  SD)
Before treatment
7 months after treatment
P-value

Group A (IL steroid)

Group B (IL BTX)

P*

2.28, 4.09  1.830

0.23, 0.77  0.749
<0.01
62.592, 82.74  8.652

1.48, 4.02  2.423

0.13, 0.9  0.875
<0.01
6094, 79.24  12.208

33, 3  0
01, 0.167  0.389
<0.01

23, 2.92  0.289

02, 1.25  0.621
<0.01

0.328
<0.01

23, 2.92  0.289

02, 0.83  0.937
<0.01

23, 2.83  0.389

02, 0.92  0.668
<0.01

0.557
0.804

23, 2.83  0.389

02, 0.58  0.668
<0.01

23, 2.83  0.389

02, 0.833  0.718
<0.01

1
0.387

23, 2.67  0.492

02, 0.92  0.668
<0.01

13, 2.25  0.866

01, 0.25  0.452
<0.01

0.161
0.010

13, 2.67  0.651

02, 1  0.738
<0.01

13, 2.5  0.674

01, 0.33  0.492
<0.01

0.544
0.007

13, 2.5  0.674

02, 1.25  0.621
<0.01

23, 2.75  0.452

01, 0.33  0.492
<0.01

0.298
0.001

0.940
0.711
0.426

*P-value when comparing values in between both groups (independent t-test).

P-value when comparing baseline values to post-treatment values in each group (Paired t-test).

the objective parameters as well as the reduction of the

volume of the keloids in comparison with the IL steroids.
The use of IL BTA in treatment of keloids has been an
issue of dispute. The results of this study come in agreement with several previous reports that documented
the efficacy of IL BTA in the management of cases of keloids.1015,18 However, on the other hand, one study
demonstrated that neither cell proliferation/growth nor
cytokines were affected by BTA incubation.19 In the
same opposing line, another study demonstrated that IL
BTA did not result in regression of keloid tissue and
that cell proliferation and metabolism of keloid fibroblasts were not affected by BTA treatment,2 but this
study was carried out on only four patients.
In explanation to our observed results, we attributed
the high efficacy of IL BTA in the treatment of keloids
to the degrading effects of BTA on the activated dermal fibroblasts.10,11,13 BTA is involved in regulating
the fibroblast cell cycle as well as in decreasing the
transforming growth factor-b1 (TGF-b1) and the
connective tissue growth factor (CTGF) expression in

164

fibroblasts derived from hypertrophic scars.12,14 Such

researches provided the experimental background for
using intradermal BTA injection for keloids, as both
TGF-b1 and CTGF are considered as key factors in
their formation. They not only regulate cellular adhesion and growth, but also cause excessive deposition of
collagen.2022
The efficacy of the IL steroids as a line of therapy in
the management of keloids has stood the test of time
being regarded by many authors to be the first line of
therapy,4 and this study was no exception to the rule.
Steroid injections have been shown to cause keloid
regression23 by decreasing collagen and glycosaminoglycan synthesis, reducing the inflammatory process in
the wound, decreasing fibroblast proliferation, and
increasing hypoxia. Steroids may reduce plasma protease inhibitors, thus allowing collagenase to degrade
collagen and leads to a decrease in the production of
endogenous VEGF TGF-b1 and IL-1.4
However, we believe that the significant rapid amelioration of the subjective complaints achieved by the
IL BTA gives this line of therapy an edge over the IL

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IL BTX in keloids

steroids. This could be explained by the ability of the IL

BTA to immobilize the local muscles and reduce the
skin tension caused by muscle pull 5 and therefore
neutralizes the small-fiber neuropathy which is typically present in keloids causing itching, pain, and allodynia.24 This was reflected on the higher patient
satisfaction score achieved by this group of patients.
Another favorable aspect for the use of IL BTA is the
complete absence of side effects, whereas skin atrophy
and telangiectasia were evident in three patients (25%)
of those receiving the IL steroids. On the other hand,
the significantly higher cost of the IL BTA is a drawback that could limit the use of this line of therapy as
a routine. Still, its inclusion in different combination
protocols, for example, with IL steroids could be a wise
solution, so as to ameliorate the potential side effects
and drawbacks of both procedures.
An intriguing question would be the potential effect
of BTA on the normal skin. Even though the fear of
atrophy might seem logical, and although the effects
are controversial, some physicians have noted a facelifting effect after intradermal injection of BTA. They
documented that BTA did not stimulate proliferation of
fibroblasts but increased the free carboxy-terminal peptide of procollagen type 1 (PIP) that quantified the
amount of collagen that fibroblasts treated with BTA
synthesize. It also stimulated the expression of type I
collagen in human dermal fibroblasts. It decreased the
production of some forms of matrix metalloproteinases.10 This points to the possibility of BTA having different effects on fibroblasts depending on their activity,
being stimulating on the normally active fibroblasts
and degrading on the highly active ones. Still such a
theory is in need of further clarification.

Conclusion
Management of keloids has transitioned from invasive
methods, including gross excision, to IL and topical
therapies that act at a cellular level. The current work
establishes the possible effective and safe off-label use
of BTA in such an indication. Further randomized controlled trials are needed to establish clear guidelines
regarding best and most cost-effective dosing, frequency of injection, and possible combination of IL
BTA in the treatment of this condition.

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