LETTERS AND COMMUNICATIONS
Role of Hyaluronidase in the Treatment of Hypertrophic Scars
Background
Hypertrophic scars develop after injuries, burns, sur-
gery, and inflammatory processes. Their treatment
remains a challenge.
Hyaluronidases are a group of enzymes catalyzing
depolymerization of hyaluronan, and consequently
remodeling the extracellular matrix (ECM). We
investigated the possibility of using commercial
hyaluronidase in the treatment of hypertrophic
scars.
Between 2012 and 2015, 21 patients (18 women and 3
men) aged between 21 and 60 years, mean age 33.95
years, SD 6 9.79 with hypertrophic scars were treated
with hyaluronidase injections (4–12 sessions) for 1 to
4 months with 1 to 4-week intervals. All patients
had at least 6 months or a longer history of the lesion.
In 6 patients, a hypertrophic scar was previously
excised more than 1 year before and had subsequently
reoccurred.
The study protocol conformed to the ethical guidelines
of the 1975 Declaration of Helsinki. All patients gave
written informed consent for the treatment and had
preliminary skin testing for hypersensitivity with 3 U
of hyaluronidase solution injected intradermally.
Clinical photographs were taken before, during, at the
end of the treatment, and 6 to 12 months after the last
injection.
Desinfiltral (Aesthetic Dermal S.L., Spain, ovine
origin) 1,500 IU reconstituted in 3 mL of sterile
0.9% saline was used in quantities up to 1,000 IU
per scar per session, depending on the volume of
the lesion. Injections were performed with
a 30 G needle directly into the base of the
scar and more superficially, so the
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ISSN: 1076-0512 Dermatol Surg 2017;0:1–3 ·
© 2017 by the American Society for Dermatologic Surgery, Inc. Published by Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
whitening of the scar was visible immediately after
the procedure.
Data were summarized as mean and SD. Statistica 12
software was used to analyze changes in scar height by
Student t test. A p value < .05 was considered statis-
tically significant.
One female patient was excluded from the study
because of a local allergic-like reaction (localized
itching and vasodilation that appeared 30 minutes
after the second injection in the region of the injected
scar). The reaction resolved within 24 hours after
subcutaneous application of 100 mg of
hydrocortisone.
The location of the scars varied from the face (cheek n
= 2, lip n = 2) and the neck (n = 3), through the chest (n
= 3), abdomen (n = 6), and buttocks (n = 1) to the thigh
(n = 2) and shin (n = 1). Complications were limited to
mild and transient swelling, bruising, and tenderness
at the injection site. Symptoms resolved spontaneously
within 24 to 48 hours.
All treated hypertrophic scars were observed to
become softer, and the softness remained in all the
patients. The patients who complained of pruritus,
redness, and pain at the end of the treatment became
asymptomatic. The average time for the treatment was
13.5 weeks (5–20), whereas the mean number of
injections was 5.6 (4–8). In the course of the treatment,
the color of the lesion improved gradually from
grayish, reddish, or whitish in old hypertrophic scars
to pinkish, more skin-like in all treated scars (Figure
1A–C). However, the whitish color did not disappear
completely, in comparison with the reddish-grayish
appearance, which improved significantly, and the
improvement was maintained at the last follow-up
visit.
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 LETTERS AND COMMUNICATIONS
Figure 1. (A) A scar from a childhood after excision of a nevus on the thigh in a 21-year-old woman before treatment. (B)
The same scar after 4 injections of hyaluronidase in 2-week intervals, 1 month since the last injection. (C) The same scar
after 6 hyaluronidase injections, 1 year since the last injection.
The mean height of the lesion also improved signifi-
cantly after treatment. It declined from 1.369 (SD 6
0.033) to 0.016 (SD 6 0.037), p < .001.
There was no correlation between the height of the
scar before the treatment and a number of injections (r
= 0.013).
Discussion
Hypertrophic scars are characterized by an altered
ECM. Hyaluronan plays an essential role during the
proliferative phase of wound healing and ECM syn-
thesis.1 Hyaluronidase regulates the level of hyalur-
onan mostly by its degradation, but its role in wound
healing processes is less obvious. It was suggested that
low molecular weight hyaluronans, the products of
hyaluronidase degradation action, stimulate angio-
genesis, the process undoubtedly contributing to
wound healing.2
In this study, we found that hyaluronidase injections
resulted in significant reduction in the size of the lesion
and complete relief of pain and pruritus. The result
was maintained even at 1 year after the last injection.
Pain and pruritus were the first symptoms to gradually
disappear, whereas the color and the size of the lesion
were the most difficult characteristics to eradicate. The
results are especially promising in patients with a his-
2 DERMATOLOGIC SURGERY
© 2017 by the American Society for Dermatologic Surgery, Inc. Published by Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
tory of hypertrophic scar reoccurrence after excision.
The hyaluronidase injections were well tolerated by all
the patients but 1 who developed an allergic-like
reaction. According to the literature, adverse effects of
hyaluronidase are uncommon. Lee in a review article
on hyaluronidase usage reported that only 0.1% of
patients receiving hyaluronidase developed urticaria
or angioedema, whereas anaphylactic-like reactions
were observed rarely, only after retrobulbar block.3 In
our patients, we observed merely mild angioedema in
1 case (4.8%).
Hyaluronidase therapy led to changes in the scar
consistency, feeling much softer, more like adjacent
skin; its borders became much less obvious. All treated
scars diminished in height significantly, independently
of their pretreatment elevation. Our results are con-
sistent with the treatment outcomes published by
Loladze.4
A possible factor affecting the success rate might be the
dose of hyaluronidase. In our study, its regulation
depended on the size of the hypertrophic scar. The
disadvantage of treatment with hyaluronidase is that
multiple visits over a relatively long period are
required to obtain satisfactory results. In our study
sample, we did not observe any deterioration in the
outcomes of treatment over a 1-year follow-up period.
 LETTERS AND COMMUNICATIONS

There were no side effects, such as skin thinning, 4. Loladze M, Alibegashvili M, Turmanidze TS, Iashvili B, et al. Use of
bilidase for the treatment of experimental hypertrophic postburn
discolorations, or telangiectasias in any of our cicatrices. Bull Exp Biol Med 2005;139:98–100.
patients.
Renata Tabola, MD, PhD
In conclusion, the treatment of hypertrophic scars Katarzyna Augoff, PhD
with hyaluronidase might be a good alternative to Krzysztof Grabowski, MD, PhD
other methods. However, the mechanisms of its Department of Gastrointestinal and General Surgery
action are poorly understood, as is scar tissue Medical University in Wroclaw
formation. Poland
References
1. Fronza M, Caetano GF, Leite MN, Bitencourt CS, et al. Hyaluronidase
Roberto Cirocchi, MD, PhD
modulates inflammatory response and accelerates the cutaneous wound Department of General and Oncological Surgery
healing. PLoS One 2014:13:e112297.
University of Perugia
2. Bitencourt CS, Pereira PA, Ramos SG, Sampaio SV, et al. Hyaluronidase
recruits mesenchymal-like cells to the lung and ameliorates fibrosis.
Italy
Fibrogenesis Tissue Repair 2011;13:3–16.

3. Lee A, Grummer SE, Kriegel D, Marmur E. Hyaluronidase. Dermatol The authors have indicated no significant interest with
Surg 2010;36:1071–7. commercial supporters.

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© 2017 by the American Society for Dermatologic Surgery, Inc. Published by Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.