Journal of Plastic, Reconstructive & Aesthetic Surgery (2011) 64, 892e897

Clinical experience with Hyaluronic

acid-filler complications*
Tae-Hwan Park, Sang-Won Seo, June-Kyu Kim, Choong-Hyun Chang *

Department of Plastic and Reconstructive Surgery, Kangbuk Samsung Hospital, Sungkyunkwan University School
of Medicine, 108 Pyung-Dong, Jongno-Gu, Seoul 110-746, South Korea

Received 9 December 2010; accepted 11 January 2011

KEYWORDS Summary Hyaluronic acid (HA) fillers have become the material of choice for soft-tissue
Soft-tissue filler; augmentation. HA fillers are longer lasting, less immunogenic and can be broken down by hyal-
HA filler; uronidase. These advantages make HA fillers the most common of the temporary fillers on the
Hyaluronic acid market. However, early and delayed complications, ranging from minor to severe, can occur
following HA-filler injection. We evaluated and treated 28 cases of HA-filler-related complica-
tions that were referred to our hospital over a period of 5 years from July 2004 to October
2009. Twenty-eight patients were included in our study; 82.1% of the patients were female
and 17.9% were male. Complications were roughly classified as nodular masses, inflammation,
tissue necrosis and dyspigmentation. Affected locations, in descending order of frequency,
were the perioral area, forehead, including glabella, nose, nasolabial fold, mentum, including
marionette wrinkles, cheek area and periocular wrinkles. The most disastrous complication
was alar rim necrosis following injection of the nasolabial fold. We propose two ‘danger zones’
that are particularly vulnerable to tissue necrosis following filler injection: the glabella and
nasal ala. Although there is no definite treatment modality for the correction of HA-filler
complications, we have managed them with various available treatment modalities aimed at
minimising patient morbidity.
ª 2011 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by
Elsevier Ltd. All rights reserved.

The use of diverse soft-tissue fillers has recently been

introduced to cosmetic surgery. The apparent simplicity of
*
filler injection and high patient satisfaction has led to
Presented at the 10th KoreaeJapan Congress of Plastic and
cavalier attitudes towards these treatments. Hyaluronic
Reconstructive Surgery, in Busan, Korea, 16e18 June 2010, and
at the 67th Annual Meeting of the Korean Society of Plastic and
acid (HA) fillers are becoming the material of choice for use
Reconstructive Surgeons, in Seoul, Korea, 19e21 November 2009. in cosmetic soft tissue and dermal correction. HA fillers are
* Corresponding author. Tel.: þ82 02 2001 2178; fax: þ82 02 2001 longer lasting, less immunogenic and more convenient than
2177. other soft-tissue fillers, and represent the largest portion of
E-mail address: [email protected] (C.-H. Chang). the temporary dermal-filler market. Since the approval of

1748-6815/$ - see front matter ª 2011 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.
doi:10.1016/j.bjps.2011.01.008
Hyaluronic acid filler complications 893

the first HA filler, Restylane, at least 10 HA fillers have been

Table 1 Patient’s characteristics
approved by the Food and Drug Administration (FDA). Not all
of the approved HA fillers are currently available, though Total Patients
many will be available in the future. The breakdown of HA by (nZ28)
hyaluronidase is an important feature and a major advantage
Age, years 33.710.1 (range,
over other medical fillers.1 With the increased use of HA
21 to 58 years)
fillers, we expect the prevalence of related complications
to increase. The purpose of this report is to share our experi- Gender
ence with 28 cases of HA-filler complications. Female, n (%) 23 (82.1%)
Male, n (%) 5 (17.9%)
Patients and methods Anatomical locations
Oral region, n (%) 5 (17.9%)
A retrospective chart review of patients treated by the senior Forehead including glabella, n (%) 5 (17.9%)
author over a period of 5 years, from July 2004 to October Nose, n (%) 4 (14.3%)
2009, was performed. We compiled and analysed data for 28 Nasolabial fold, n (%) 4 (14.3%)
patients, who underwent various treatments secondary to Mentum, n (%) 3 (10.7%)
HA-filler complications at our hospital. We reviewed data Cheek area, n (%) 3 (10.7%)
including symptoms, gender, age, interval between the time Periocular winkles, n (%) 2 (7.1%)
of injection to the first visit, type of practitioner performing
the injection, previous treatment history, anatomical loca- Main symptoms
tions of injection and treatment methods. Patients were Nodular mass, n (%) 12 (42.9%)
followed up after their last procedure, and their outcomes Inflammatory symptoms, n (%) 10 (35.7%)
were evaluated by asking the patients to rate their overall Tissue necrosis, n (%) 3 (10.7%)
satisfaction on a scale from 1 (worse) to 5 (excellent) using Dyspigmentation, n (%) 3 (10.7%)
a 10-item questionnaire that was developed and has been The type of practitioners
used in our hospital since 2003. Plastic surgeons, n (%) 9 (32.1%)
Dermatologists, n (%) 9 (32.1%)
General physicians, n (%) 10 (35.7%)
Results
Values are mean  SD for continuous variables and number
(percentages) for categorical variables
Patient’s characteristics (Tables 1 and 2)

Of the total 28 patients, 23 (82.1%) were women and five hyaluronidase injection. She complained of palpable mass
were men (17.9%). The average age was 33.7 years (range, of her lower lip. We treated her with one operation, and
21e58 years); most patients were between the ages of 21 the patient was very satisfied with the correction of lip
and 30 years. Symptoms were diverse, but were roughly contour (Figure 1).
classified as: 12 patients (42.9%) with a nodularity or
palpable mass, 10 patients (35.7%) with inflammatory Case II
symptoms such as swelling, tenderness and redness, three The second patient was a 56-year-old woman with inflam-
patients (10.7%) with tissue necrosis, including one case matory signs of nasal tip. She had a history of HA-filler
of alar rim involvement and three patients (10.7%) with dys- injection about 1 year prior, and had a history of treatment
pigmentation. The average time interval between HA-filler using hyaluronidase. We treated her with conservative
injection and first visit was 5.3 months. Practitioners, who treatment using warm massage with oral antibiotics and
gave the original injections, included nine (32.1%) plastic the treatment was successful (Figure 3).
surgeons, nine (32.1%) dermatologists and 10 (35.7%)
general physicians. Case III
The anatomic locations, in order of frequency, were the The third patient was a 43-year-old woman with persistent
oral region, including the lips and oral commissure (five swelling of her both lower eyelids after HA-filler injection
patients, 17.9%, Figure 1), forehead, including glabella (five about 6 months prior (Figure 6). She was in therapy with
patients, 17.9%, Figure 2), nose (four patients, 14.3%, oral antibiotics and underwent laser therapy at other
Figure 3), nasolabial fold (four patients, 14.3%), mentum, hospital. She underwent foreign body removal via a lower
including marionette wrinkles (three patients, 10.7%, blepharoplasty incision and was satisfied with the outcome
Figure 4), cheek area (three patients, 10.7%, Figure 5) without any recurrence up to present time (Figure 7).
and periocular wrinkles (two patients 7.1%; Figure 6).
Discussion
Three selected clinical cases
HA is a glycosaminoglycan polysaccharide composed of
Case I alternating residues of the monosaccharide d-glucuronic
The first patient was a 23-year-old woman with palpable acid and N-acetyl-d-glucosamine that is normally present
mass of her lower lip after injection of HA filler about 3 in the human body.2 Apart from its moisturising function,
years prior. She had a history of treatment through HA plays a major role in wound healing and acts as
894 T.-H. Park et al.

Table 2 Patient’s characteristics

Case # Anatomical location Main symptom Onset of treatment after HA injection Treatment
1 Forehead Nodularity 24 months Surgical excision
2 Nasal sidewall Tissue necrosis 3 months Oral antibiotics
3 Nasal tip Redness 2 weeks Hyaluronidase
4 Forehead Nodularity 3 months Hyaluronidase
5 Forehead Tenderness, redness 2 months Oral antibiotics
6 NLF Discolouration 6 months Observation
7 Mentum Tissue necrosis 12 months Surgical excision
8 Lower eyelid Nodularity 6 months Surgical excision
9 Crow’s feet Redness 3 weeks Oral antibiotics
10 NLF Alar necrosis 1 week Oral antibiotics
Hyaluronidase
11 NLF Discolouration 3 months Hyaluronidase
12 Upper lip Nodularity 6 months Hyaluronidase
13 Lower lip Palpable mass 3 years Surgical excision
14 Both cheek Palpable mass 12 months Surgical excision
15 Forehead Swelling, tenderness 2 weeks Hyaluronidase
Oral antibiotics
16 Oral commissure Redness 2 weeks Oral antibiotics
17 Oral commissure nodularity 2 months Hyaluronidase
18 Upper lip palpable mass 12 months Oral antibioticsþ
Surgical excision
19 Lower lip Nodularity 15 month Surgical excision
20 Marionette wrinkle Erythema 1 month Oral antibiotics
Swelling
21 Both cheek Redness 2 week Oral antibiotics
22 Mentum Palpable mass 24 months Surgical excision
23 Lower lip Nodularity 1 month Hyaluronidase
24 Both cheek Palpable mass 2week Hyaluronidase
25 Forehead Nodularity 2week Hyaluronidase
26 NLF Discolouration 3 months Observation
27 Nose Swelling, tenderness 2 week Hyaluronidase
28 Nasal tip Redness 2 months Oral antibiotics

a free-radical scavenger. Adverse events can be grouped area by direct injury to the vasculature, compression of
into procedure-related events, such as bruising, erythema vasculature or direct obstruction of the vessel by the HA
and tenderness, events potentially related to improper filler secondary to its hydrophilic action. To prevent these
technique, such as a nodule formation and reactions to disastrous complications, plastic surgeons should be
the product, such as granuloma formation. The most severe familiar with potentially dangerous injection zones and
and feared early-occurring complication is tissue necrosis, facial anatomy. We suggest two such dangerous zones
possibly due to interruption of the vascular supply to the susceptible to tissue necrosis: the glabella and nasal ala.3

Figure 1 Palpable mass of the lower lip and gross specimen.

Hyaluronic acid filler complications 895

Figure 2 Multiple nodularities of the forehead.

Figure 4 Dyspigmentation with palpable mass of the
Injections into these sites should be done with caution, as mentum.
these areas have limited collateral circulation. Vascular
compromise resulting in necrosis and, rarely, blindness The injector should be well trained in injection technique
has been reported following injections at the glabella.3 and correctly identify which filler to implant at what depth.
Alar necrosis associated with HA-filler injections is infre- The most common, and minor, inflammatory reactions,
quently reported.4 Aspiration prior to injection, use of such as swelling, tenderness or redness, are easily managed
small amounts of filler and proper injection techniques with the application of ice. In cases that are suspicious for
may further decrease this risk. Direct arterial embolisation bacterial infection, we routinely treat with oral antibiotics.
of filler can be recognised by immediate, often severely Nodules are caused by excess filler or may be the result of
painful geographic blanching. Treatment options include inflammation and/or granuloma formation. In cases of
attempted aspiration, application of 2% nitroglycerin paste, nodules or palpable masses (<6 months), we empirically
injection of hyaluronidase and warm compresses. Venous inject hyaluronidase, with or without oral antibiotics.
occlusion is often delayed, and presents as a dull pain Hyaluronidase is effective for treating bumps and over-
with bluish discolouration that may simulate a bruise. injection of HA. Hyaluronidase dissolves the peptide bonds
There are several important factors that may influence in long-chain proteins within HA, increasing the mobility of
the occurrence of adverse events. Prior to injecting any the injected viscoelastic material and allowing it to
dermal filler, a thorough medical history, including medi- disperse more freely as oligoproteins through the tissue.
cation, allergies and scarring history should be obtained. Although treatment with hyaluronidase is effective,
outcomes are unpredictable and sometimes transient;
detailed explanations must be provided to the patient
regarding the pros and cons prior to treatment. Numerous

Figure 3 Inflammation of the nasal tip. Figure 5 Inflammation of the left cheek.
896 T.-H. Park et al.

as numerous variables, such as patient emotional state,

underlying psychological disease and doctorepatient rela-
tionships, may affect outcomes. Lastly, there was a lack of
multiple follow-up time points to better track patient
status secondary to follow-up losses of patients with
minimal symptoms.

Figure 6 Persistent swelling of the both lower eyelid

Conclusions

We stress the importance of cautious medical-filler injec-

tion and public education regarding the potentially disas-
trous consequences of unregulated filler injection. With
several HA fillers already available, the potential benefits
that patients may receive from the release of additional
HA-derived fillers must be carefully weighed against the
risks. Among the various complications, tissue necrosis is
the most serious. The glabella and nasal ala may be
particularly vulnerable regions due to vascular anatomy.
Among the various treatment modalities for HA injection
complications, there is no significantly superior option.
With HA fillers specifically, hyaluronidase injections offer
a further treatment option. Additional study of HA fillers is
required to reduce the occurrence of adverse reactions.

Figure 7 Foreign body removal via a subciliary incision. Conflict of interest

None of the authors has any financial and personal relation-

treatment methods, including application of ice, warm ships with other people or organisations that could inap-
massage, oral antibiotics, intralesional hyaluronidase injec- propriately influence this article.
tion, laser treatment and surgical excision, have been
performed for various HA injection-related complications
and presentations, suggesting that no single method is yet
References
an accepted standard of care.
1. Menon H, Thomas M, D’Silva J. Low dose of Hyaluronidase to
One of the strengths of this report is its relatively large
treat over correction by HA fillerea case report. J Plast Reconstr
patient sample. However, this report also has limitations.
Aesthet Surg 2010;63:e416e7.
First, this study was a cross-sectional, retrospective study 2. Andre P. Hyaluronic acid and its use as a “rejuvenation” agent in
and is therefore limited in its ability to assess changes in cosmetic dermatology. Semin Cutan Med Surg 2004;23:218e22.
satisfaction over time. Second, our patients suffered from 3. Glaich AS, Cohen JL, Goldberg LH. Injection necrosis of the
relatively severe complications when compared with those glabella: protocol for prevention and treatment after use of
described in most other reports. For these reasons, our dermal fillers. Dermatol Surg 2006;32:276e81.
results cannot be generalised to patients in all circum- 4. Judd O, Gaskin J. Securing the posterior nasal pack; a technique
stances. Third, our results may be affected by response bias to prevent alar necrosis. Ann R Coll Surg Engl 2009;91:713e4.

INVITED COMMENTARY

Complications of hyaluronic acid injections

or something else?
M. Felix Freshwater *

University of Miami School of Medicine, Surgery, 9100 S. Dadeland Blvd. Ste. 502, Miami, FL 33156-7815, United States

Received 10 February 2011; accepted 13 February 2011