Analysis of U.S.

Food and Drug Administration Data on

Soft-Tissue Filler Complications
Arisa E. Ortiz, MD,* Jusleen Ahluwalia, MD,* Silvia S. Song, MD,† and
Mathew M. Avram, MD, JD‡

BACKGROUND With the rising popularity of dermal fillers, the number of complications associated with
fillers has increased.

OBJECTIVE To identify and review reports of adverse events involving cosmetic injectable soft-tissue fillers
from the FDA Manufacturer and User Facility Device Experience (MAUDE) database from June 1993 to August
2014.

MATERIALS AND METHODS The authors conducted a search of adverse events within the U.S. Food and Drug
Administration database that involved injectable dermal fillers for soft-tissue augmentation from June 1993 to
August 2014. Search terms included generic and trade names of commercially available soft-tissue fillers.

RESULTS Three thousand seven hundred eighty-two complications involving dermal fillers were identified in the
MAUDE database. Forty-four percent of complications implicated hyaluronic acid fillers, 40% involved poly-L-lactic
acid fillers, 15% complications included calcium hydroxylapatite fillers, and <1% complications arose from poly-
methylmethacrylate fillers. Common adverse events included lumps, infection, allergic reaction, ischemia, and
swelling. Rare events included trigger of autoimmune reactions, visual disturbances, and stroke.

CONCLUSION Although complications with dermal fillers are infrequent in comparison with the growing
number of filler procedures being performed in the United States every year, this study underscores the importance
of appropriate skill and training when administering dermal fillers. Physicians using injectable dermal fillers should
be trained to recognize potential complications and know how to appropriately manage them.

A.E. Ortiz is a consultant for Alastin and Cutera. M.M. Avram is a consultant for Alastin, Allergan, Merz, Sciton,
Sienna and Soliton. The remaining authors have indicated no significant interest with commercial supporters.

ermal fillers have been used to volumize and
D contour the face with a high rate of patient
satisfaction. According to an American Society for
Dermatologic Surgery (ASDS) survey on dermatologic
procedures, of a total of 12 million cosmetic and
medically necessary procedures, 1.6 million soft-tissue
filler procedures were performed by dermatology
members in 2017.1 This number increased by 21%
from the number of procedures performed a year
prior, which represents the largest year-to-year growth
reported to date.1 More procedures are being
performed by other specialties and nonphysicians, as
well.
Adverse events associated with fillers can be seen
within days (early onset) or after weeks to years (late
onset). Early-onset complications include injection-
site reactions, infection, hypersensitivity, morpholog-
ical problems (lumps and asymmetries), skin discol-
oration, vascular occlusion, and blindness.2 Late-
onset complications include infection, foreign body
granuloma, migration, immune reactions, persistent
discoloration, and scarring.2 Rarely, cerebral ischemic
events have also been reported to occur.2
It is useful to assess the types and frequency of adverse
events that may help clinicians guide patient

*Department of Dermatology, University of California, San Diego School of Medicine, La Jolla, California; ‡Dermatology
Cosmetic and Laser Center, Harvard Medical School, Massachusetts General Hospital, Boston, Massachusetts; †Kaiser
Permanente, Anaheim Hills, California

© 2019 by the American Society for Dermatologic Surgery, Inc. Published by Wolters Kluwer Health, Inc. All rights reserved.
· ·
ISSN: 1076-0512 Dermatol Surg 2019;00:1–5 DOI: 10.1097/DSS.0000000000002208

© 2019 by the American Society for Dermatologic Surgery, Inc. Published by Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
 FDA DATA ON FILLERS

discussions and promote awareness of potential
complication risks depending on the location site, type
of filler used, etc. Until recently, there has been a
paucity of studies that evaluate the incidence of com-
plications associated with dermal fillers. This is the
largest review of the Manufacturer and User Facility
Device Experience (MAUDE) database categorizing
adverse events related to filler procedures.
The U.S. Food and Drug Administration’s (FDA’s)
MAUDE database houses reports of adverse events
involving medical devices and procedures submitted
to the FDA. This public repository is federally fun-
ded and updated monthly with reports submitted by
user facilities, distributors, and manufacturers since
the early 1990s. This database may be searched by
the year of procedure, manufacturer, brand name,
generic name, or product class to explore reports of
interest. Reports include a narrative description
from which complications can be identified. Data
are not available regarding the patient’s sex, age,
confirmation of complication diagnosis, or injector.
Reports may be entered by anyone and may not be
complete. Nevertheless, the MAUDE database is the
largest database for soft-tissue filler complication
reports in the world.
Methods
The MAUDE database was queried for adverse events
involving injectable dermal fillers reported from June
1993 to August 2014. Search terms included generic
and brand names of commercially available dermal
fillers, as follows (generic name [brand name]):
adverse event narratives pertaining to dermal fillers
were reviewed by AEO or SK. No reports were dis-
carded. Data were summarized descriptively and pre-
sented in a tabular and chart format. Certain products
that are currently commercially available were not
included in the search because these products were not
available in the queried years. For example, Juvéderm
Volbella, Juvéderm Vollure, Restylane Refyne,
Restylane Defyne, and Restylane Lyft were not
included in the search terms because these received
FDA approval after 2014.
Results
A total of 3,782 adverse events were reported in the
MAUDE database from June 1993 to August 2014. Of
these, 1,677 reports (44%) were related to hyaluronic
acid fillers, 1,517 reports (40%) were related to poly-L-
lactic acid, 572 reports (15%) were related to calcium
hydroxylapatite, and 16 reports (<1%) were related to
polymethylmethacrylate. Specific brand name filler-
related adverse events are listed in Table 1.
Of all adverse events reported, lumps were the most
frequently reported (39.2%), followed by infection
(12.9%), and swelling (10.2%). When stratified by
the filler, lumps were the most frequently reported
in cases describing use of hyaluronic acid, poly-
methylmethacrylate, and poly-L-lactic acid soft-
tissue fillers (Figure 1A–D). By contrast, vascular
compromise was the most commonly reported
TABLE 1. Risk Profile Associated With Brand
Name Fillers

• Hyaluronic acid (Belotero, Elevess, Hydrelle, Filler

Hylaform, Juvederm [Juvéderm 24HV, Juvéderm Juvéderm 517
30, Juvéderm 30HV, Juvéderm Voluma, Juvéderm Perlane 65
Ultra XC, Juvéderm Ultra Plus XC], Perlane, Restylane 236
Belotero 6
Prevelle, Restylane [Restylane Silk, Restylane
Elevess 109
injectable gel, Restylane-L]) Hydrelle 181
• Poly-L-lactic acid (Sculptra) Hylaform 74
• Calcium hydroxylapatite (Radiesse) Prevelle 29
• Polymethylmethacrylate (Artefill) Sculptra 1,638
Radiesse 478
Data on report date, complication type, filler used, and Artefill 13
Total 3,782
location of injection (if applicable) were collected. All

2 DERMATOLOGIC SURGERY

© 2019 by the American Society for Dermatologic Surgery, Inc. Published by Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.

Figure 1. (A–D) Adverse events associated with soft-tissue fillers.
complication in events involving calcium hydroxyl-
apatite fillers (Figure 1B). Infection was reported in
488 reports (12.9%) and was characterized as bac-
terial, viral (herpes or varicella), or fungal in etiology.
Vascular necrosis represented 8.5% of all complica-
tions related to the dermal filler procedure. Of all
reported cases of vascular necrosis, injection into the
nasolabial fold (NLF) was associated with the highest
number of cases of vascular necrosis (36.9%) followed
by injection into the nose (19.7%) (Figure 2).
Development of systemic symptoms was reported as a
complication in 35 cases (0.9%) and included gas-
trointestinal bleeding, renal failure, sarcoidosis, diz-
ziness, flu-like symptoms, and shortness of breath.
Moreover, triggers of autoimmune disorder, such as
polymyalgia, scleroderma, Graves disease, Guillain–
Barré syndrome, and rheumatoid arthritis, were noted
© 2019 by the American Society for Dermatologic Surgery, Inc. Published by Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
ORTIZ ET AL
in 27 cases (0.7%). Allergic reactions (anaphylaxis,
hives, laryngoedema, angioedema, and shock) after
injection were noted in 207 reports (5.5%), of which
approximately two-thirds were related to adminis-
tration of hyaluronic acid.
Three reports (0.1%) described cases of cerebrovas-
cular injury after hyaluronic acid filler to the NLF, lips,
forehead, and chin. There were 56 reports (1.5%) of
visual disturbances (hyaluronic acid filler, n = 21; poly-
L-lactic acid, n = 25; polymethylmethacrylate, n = 2;
and calcium hydroxylapatite, n = 8). Three reports
(0.1%) included death and involved hyaluronic acid,
polymethylmethacrylate, and poly-L-lactic acid fillers.
Discussion
Around 1 million total soft-tissue filler procedures
were performed in 2014 alone.1 In 2010, ASDS
00:00:MONTH 2019 3
 FDA DATA ON FILLERS
Figure 2. Vascular necrosis by location of dermal filler injection. NLF, nasolabial fold.
members performed approximately 838,827 soft-
tissue filler procedures, using Juvéderm (Allergan,
Dublin, Ireland) (68% of members), Restylane (for-
merly Perlane) (Galderma, Lausanne, Switzerland)
(61% of members), Radiesse (Merz Pharmaceuticals,
Raleigh, NC) (50% of members), and Sculptra (Sanofi,
Paris, France) (35% of members).1 Our study included
3,782 records of dermal filler complications, of which
the most frequently reported dermal filler in our study
was hyaluronic acid-based, likely because hyaluronic
acid was the most commonly used filler at that time.1
In another analysis conducted by Rayess and col-
leagues,3 1,748 reports of dermal filler use were recorded
in the MAUDE database from January 2014 to
December 2016. The authors revealed a stark difference
between the number of complications involving hyalur-
onic acid (1,600 reports; 92%) and poly-L-lactic acid (47
reports; 2.7%) fillers; however, this was not observed in
our study.3 This difference may be attributed to the
lapsed time between FDA approval of poly-L-lactic acid
fillers in 2004 and optimization of dilution parameters,
decreasing the incidence of adverse events associated
with poly-L-lactic acid fillers (Figure 3).
Although fillers composed of hyaluronic acid have
been deemed to be safer and thus resulted in increased
use, all fillers have been associated with complications.
Complications include ecchymosis, erythema and
edema, formation of lumps and granulomas, infec-
4 DERMATOLOGIC SURGERY
© 2019 by the American Society for Dermatologic Surgery, Inc. Published by Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
tions, systemic symptoms, and more serious events,
such as vascular occlusion. Proper technique and
incorporation of proposed methods to avoid filler
complications are essential to achieve a safe and
favorable outcome for the patient.4–8
The MAUDE’s database is the largest electronic
resource that describes adverse events associated
with fillers, although not all complications related to
filler use are reported to the MAUDE database. For
example, although pain and bruising are expected
complications, they have not been reported as fre-
quently, which is reflective of the inherent reporting
bias within the MAUDE database. Because reports
are narrative in nature, there is no standardized
template to report complications to the FDA; thus,
details surrounding reported adverse events may
vary. In addition, it is difficult to determine whether
these complications were due to errors of placement
of the dermal filler, coincidental occurrences, or
problems with concomitant procedures
(i.e., neurotoxins or surgical). Nevertheless, knowl-
edge of these complications is valuable to practi-
tioners in their attempts to prevent adverse events
associated with dermal fillers.
Conclusion
The widespread use of dermal fillers has expectedly led
to an increase in associated adverse events. The aim of

Figure 3. Number of reports of adverse events related to soft-tissue fillers over time. *FDA approval of hyaluronic acid
fillers. **FDA approval of poly-L-lactic acid fillers. ***FDA approval of polymethylmethacrylate and calcium hydroxylapatite
fillers. FDA, U.S. Food and Drug Administration.
this analysis was to describe complications involving
dermal fillers reported in the largest electronic repos-
itory and promote knowledge and awareness of
potential filler complications. Common adverse events
reported included infection, allergic reaction, and
swelling. More rare events included trigger of auto-
immune reactions, visual disturbances, blindness, and
stroke. Physicians using dermal fillers should be
trained to recognize potential complications and know
how to appropriately manage them.
References
1. ASDS Consumer Survey on Cosmetic Dermatologic Procedures.
Available from: https://www.asds.net/Medical-Professionals/Practice-
Resources/ASDS-Consumer-Survey-on-Cosmetic-Dermatologic-
Procedures. Accessed November 5, 2018.
2. Kim H, Cho SH, Lee JD, Kim HS. Delayed onset filler complication: two case
reports and literature review. Dermatol Ther 2017. [Epub ahead of print].
© 2019 by the American Society for Dermatologic Surgery, Inc. Published by Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
ORTIZ ET AL
3. Rayess HM, Svider PF, Hanba C, Patel VS, et al. A cross-sectional
analysis of adverse events and litigation for injectable fillers. JAMA
Facial Plast Surg 2018;20:207–14.
4. Urdiales-Gálvez F, Delgado NE, Figueiredo V, Lajo-Plaza JV, et al.
Treatment of soft tissue filler complications: expert consensus
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Address correspondence and reprint requests to: Jusleen
Ahluwalia, MD, 8899 University Center Lane, Suite 350,
San Diego, CA 92122 juahluwalia@ucsd.edu
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