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Received: 15 November 2019    Revised: 10 December 2019    Accepted: 16 December 2019

DOI: 10.1111/jocd.13287

C O S M E T I C C O M M E N TA R Y

Delayed skin necrosis following hyaluronic acid filler injection:

A case report

Daniel Cassiano MD1  | Tatiana Miyuki Iida MD2 | Ana Lúcia Recio MD2 |

Samira Yarak PhD1

1
Department of Dermatology, Universidade
Federal de São Paulo, São Paulo, Brazil
2
Private Office, São Paulo, Brazil
Correspondence
Daniel Pinho Cassiano, Rua Dr Diogo de
Faria, 917, Apto 223, São Paulo, SP, 04037-
003 Brazil.
Email: danielpcassiano@uol.com.br
Abstract
Vascular compromise is a rare but serious complication of dermal filler injection.
Vessel occlusion tends to have a more immediate onset of symptoms. We report a
case of skin necrosis that started with pain, erythema and edema two days after hya-
luronic acid filler on the forehead of a 57-year-old woman. The patient was treated
with less than 24 hours the onset of symptoms, leaving discreet scar. The current
theories that explain skin necrosis caused by HA fillers include angiospasm and em-
bolization. The frontal region has many anastomoses, the embolized proximal vessel
initially did not lead to symptoms. However, the HA inside the artery may have trave-
led over time and reached a terminal distal branch, which generated localized skin
damage and pain. The urgent treatment of arterial occlusion and thromboembolism
caused by HA injection is intralesional high-dose hyaluronidase.

KEYWORDS

complications, hyaluronic acid, skin necrosis

1 |  I NTRO D U C TI O N (supratrochlear, supraorbital arteries) and external carotid arteries

Hyaluronic acid (HA) fillers are an important tool in the treatment of
facial aging. Due to its popularity, HA injection has become a stan-
dard cosmetic procedure for dermatologists and plastic surgeons. In
recent years, advanced filler injection techniques have been estab-
lished that meet different patient demands. As a result, HA with dif-
ferent rheological and physicochemical profiles has been introduced
to the market, which has allowed for the selection of appropriate
products for each anatomical area of the face.1
Forehead rejuvenation is one of the most recent indications for
fillers. With aging, a loss of convexity of the forehead occurs, which
can be reversed with the use of HA. In addition, the frontal and gla-
bellar wrinkles can be filled when the effects of botulinum toxin are
limited. However, these anatomical areas are considered risk areas
for vascular complications. The vascularization of the forehead is
supplied by anastomoses of the branches of the internal carotid
(frontal branch of the superficial temporal artery).
All fillers can induce skin ischemia in any region of the face,
which is an unpredictable complication. Multiple theories have been
proposed regarding the pathogenesis of necrosis induced by HA in-
jection. 2 However, the exact mechanism is not well understood. It is
believed that several factors are involved, including vascular com-
pression, vascular damage, and microemboli that form from the in-
tra-arterial injection of the biomaterial. Thus, the final lesion would
be due to a combination of angiospasm, inflammation of the arteries,
and thrombotic occlusion of the arterioles.
The symptoms of necrosis usually occur during the injection or a
few hours after the injection. The clinical condition is called Nicolau
syndrome and is characterized by immediate pain, pallor (not always
evident), and livedoid appearance in the region, followed by ery-
thema, edema, pustules with neovascularization, and necrosis of the
skin.3

J Cosmet Dermatol. 2020;00:1–3. wileyonlinelibrary.com/journal/jocd© 2020 Wiley Periodicals, Inc.     1 |

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2       CASSIANO et al.
2 |  C A S E R E P O RT
A 57-year-old woman with no comorbidities was treated with Restylane
F I G U R E 1   Third postoperative day of hyaluronic acid injection
with 25G cannula over the temporal and frontal areas: <24 h
after the onset of pain, the skin presented pustules over an
erythematous, edematous ill-defined plaque
Vital® (Galderma) in June 2019 for rejuvenation of the frontal region.
The procedure was performed with a 25G cannula, and 0.5 mL of HA
was injected into each side in the sub-SMAS plane without complica-
tions. At the end of the procedure, the patient was released without
complaints and with care instructions. However, two days after the
filler injection, the patient developed pain, erythema, and edema in the
frontal region. Less than 24 hours after the onset of symptoms, the pa-
tient presented with erythema, edema, and pustules in the frontal re-
gion (Figure 1), with the diagnostic hypothesis of vascular obstruction.
Hyaluronidase (200 TRU) was injected throughout the treated region,
which led to immediate pain relief; the patient was also prescribed
500 mg ASA for 3 days and 40 mg prednisolone for 3 days, which was
combined with local heat application. The patient's condition improved
and progressed with minimal scarring (Figure 2).
3 | D I S CU S S I O N
In general, vascular complications arise during or immediately after
skin filling. Unlike most cases reported in the literature, the clinical
manifestation of this case showed cutaneous symptoms and signs of
necrosis two days after the procedure.
The current theories that explain skin necrosis caused by HA fill-
ers include angiospasm and embolization. The first can occur due to
multiple factors, such as compression of the vessel (by the injected
liquid or a hematoma), by direct injury of the vessel with the needle
or cannula, or by an arterio-arterial or veno-arterial reflex of immu-
noallergic origin. The second, in turn, is caused by the intra-arterial
injection of the material. Clinical and anatomopathological observa-
tions support the embolization theory because HA microparticles
were found inside the arterioles.4
In an animal model that is used to test the action of hyaluroni-
dase after embolism caused by an HA filler, it was shown that an area
F I G U R E 2   Before the procedure
and thirty days after the complication.
Residual hyperpigmentation was
noticeable
CASSIANO et al.
with a rich vascularization only undergoes necrosis if, in addition to
an arterial embolism, the flow of the other artery that irrigates the
region through the anastomoses is also obstructed.5
This phenomenon could explain the delayed development of symp-
toms in this case. As the frontal region has many anastomoses, the em-
bolized proximal vessel initially did not lead to symptoms. However, the
HA inside the artery may have traveled over time and reached a ter-
minal distal branch, which generated localized skin damage and pain.
The urgent treatment of arterial occlusion and thromboembo-
lism caused by HA injection is intralesional high-dose hyaluroni-
dase. Although in this case ASA was also used, nowadays, heparin
is most recommended as adjuvant therapy, specially the low-mo-
lecular-weight heparin (LMWH), due to its anticoagulant action and
anti-inflammatory properties. LMWH seems to limit inflammatory
cell extravasation into the thrombosed vein wall, but the mechanism
responsible for the anti-inflammatory effect is not fully understood.6
Furthermore, with the presentation of edema, erythema, and pus-
tules, empiric antibiotic therapy, ideally after pustule culture, should
have been instituted, since bacterial infection is a differential diag-
nosis and therapy cannot be delayed.
We emphasize that the use of a 25G cannula enabled the vas-
cular accident with skin necrosis. Due to this case, the authors rec-
ommend using blunt cannulas with a minimum 22 gauge for facial
skin filling. Doing so will minimize the chances of vessel cannulation
while also avoiding arterial damage, which can cause inflammation
and further contribute to the vasospasm.
The authors call attention to the importance of the diagnosis
of vascular embolism with atypical presentation given the delayed
onset of symptoms after filling. Dermatologists and plastic surgeons
must be vigilant because early treatment with hyaluronidase pre-
vents unaesthetic scars. We hope that future studies will help in-
crease the understanding of the pathogenesis of this complication.
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AC K N OW L E D G M E N T S
None.
ORCID
Daniel Cassiano  https://orcid.org/0000-0003-2615-0456
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How to cite this article: Cassiano D, Miyuki Iida T, Lúcia
Recio A, Yarak S. Delayed skin necrosis following hyaluronic
acid filler injection: A case report. J Cosmet Dermatol.
2020;00:1–3. https​://doi.org/10.1111/jocd.13287​