CASE REPORT/CLINICAL TECHNIQUES

Fatima Al-sheeb, BDS,

Nicolau Syndrome after MClinDent (Endodontology),
MRCSED, Ghanim Al Mannai,
Endodontic Treatment: A Case BDS, MMSC, and
Shailaja Tharupeedikayil, BDS,
Report General Radiography Diploma

ABSTRACT
SIGNIFICANCE
Calcium hydroxide has been used successfully in root canal therapy for many years. However,
it can cause serious damage if it is inadvertently displaced into surrounding vital structures, Despite its rarity, clinicians
resulting in thrombosis if displaced into blood vessels, damaging connective tissue, and should be aware of Nicolau
causing skin necrosis. These adverse reactions are known as Nicolau syndrome (NS) or syndrome, which might occur
embolia cutis medicamentosa. Very few case reports have been published about these by displacing calcium
adverse effects of injecting calcium hydroxide beyond the apex during root canal therapy. A hydroxide beyond the apex
16-year-old female patient was referred to the endodontic department of Hamad Dental during root canal therapy.
Center for assessment after treatment by the maxillofacial surgery department for swelling and Overinstrumentation and the
tissue necrosis that occurred after endodontic treatment in another clinic. When the patient forced injection of calcium
initially attended the maxillofacial surgery department, she presented with swelling on the left hydroxide should be avoided.
side in the region of the maxillary left first permanent molar. On examination, there was a
change in the color of the skin of the left cheek in that area along with some reported paralysis
of the left side of her lips. Analgesics and antibiotics had already been prescribed at the
referring clinic. Two weeks later, the patient developed a necrotic patch of skin on the same
area. Subsequent evaluation at the endodontic department of Hamad Dental Center led to a
diagnosis of NS. NS is a very rare iatrogenic condition. Displacing calcium hydroxide beyond
the apex might increase the chance of NS. Clinicians should avoid overinstrumentation and
forced injection of calcium hydroxide to prevent NS. (J Endod 2022;48:269–272.)

KEY WORDS
Calcium hydroxide; complication; Nicolau syndrome; tissue damage; vascular thrombosis

Calcium hydroxide (CH) has been successfully used as an interim dressing during root canal treatment
because of its antiseptic properties and low toxicity1. It contributes to a high degree of success of root
canal therapy. Nonetheless, CH can cause serious damage and have long-lasting consequences if
displaced into the soft tissue or vessels2–6.
The damaging effects of CH when displaced into the inferior alveolar nerve or an artery adjacent to
a molar root apex have been described in previous studies2,3,6,7. A case of thromboses of the inferior
alveolar artery, various branches of the maxillary artery, and skin necrosis resulting from accidental
injection of CH into the soft tissue was reported in 20113. It was diagnosed as embolia cutis
medicamentosa or Nicolau syndrome (NS). This syndrome was first described in 1925 as a rare
cutaneous adverse reaction at the site of an intramuscular or intra-articular injection of a particular drug8. From the Hamad Dental Center, Hamad
NS is characterized clinically by severe pain immediately after the injection followed by an erythematous, Medical Corporation, Doha, Qatar
reticular patch that subsequently progresses to a necrotic ulcer and scarring at the injection site9. Address requests for reprints to Fatima Al-
To date, the adverse reactions of displaced CH during root canal therapy have been published in a sheeb, Hamad Dental Center, Hamad
Medical Corporation, PO Box 3050,
relatively limited number of case reports and case series6. The purpose of this article was to report an
Doha, Qatar.
incident of NS after injecting CH beyond the apex of tooth 14 during endodontic treatment. E-mail address: falsheeb1@hamad.qa
0099-2399

CASE REPORT Copyright © 2021 The Authors. Published

by Elsevier Inc. on behalf of American
A 16-year-old female presented to the Department of Maxillofacial Surgery at Hamad Dental Center in Association of Endodontists. This is an
Doha, Qatar, after receiving root canal treatment at another clinic. The patient reported that during her open access article under the CC BY-NC-
ND license (http://creativecommons.org/
second visit for the endodontic treatment of tooth 14, treatment was commenced without local licenses/by-nc-nd/4.0/).
anesthesia. According to the patient’s documentation at the clinic, after preparation the canals began to https://doi.org/10.1016/
bleed profusely, and because of increasing pain, the dentist administered local anesthesia. The canals j.joen.2021.10.006

JOE  Volume 48, Number 2, February 2022 Nicolau Syndrome after Endodontic Treatment 269
were then injected with unset CH in an attempt
to stop the bleeding, but the patient then
began to experience severe pain and a slight
change of the skin color on her left cheek in the
region of the maxillary left first permanent
molar. The brand name of the unset CH and
the syringe gauge used were not documented.
By the following day, swelling had developed in
the area where the skin had changed color.
She returned to the same clinic where
antibiotics and analgesics were prescribed and
the unset CH was washed out. The patient
was then referred to the maxillofacial surgery
department at Hamad Dental Center for
consultation.
Three days after the root canal
treatment, the patient presented to the FIGURE 1 – Skin necrosis in the left infraorbital area after 2 weeks following endodontic treatment of tooth 14.
maxillofacial surgery department with a slight
swelling and an associated hematoma on the
vasculature. It can be hypothesized that the fat, and muscle develop necrosis or an ulcer
left cheek. The patient also reported paralysis
extrusion of the CH caused direct trauma to and subsequently heal with scar formation.
on the left side of the lips and excessive tearing
the vascular structures. Inflammation of the The patient in the present case report exhibited
from the left eye (epiphora). Seventeen days
arteries and arterial embolism due to the same clinical features.
later, the patient again presented to the
crystallization of the drug occurred, leading in In an attempt to clarify the clinical
maxillofacial surgery department with a
turn to ischemia and local necrosis. These features of NS, Brachel and Meinertz15
necrotic patch of skin in the left infraorbital/
clinical features are described as NS12. experimented on rabbit earlobes in 1977. They
molar region that was approximately 4 ! 4 cm
NS, or embolia cutis medicamentosa, is injected a phenylbutazone solution into the
(Fig. 1). A plastic surgery appointment was
a very rare iatrogenic condition that is currently para-arterial, intra-arterial, and para-arterial
arranged to assess and treat this necrotic
not well understood12. NS is an uncommon areas after the perforation of the vessels. The
patch. In addition, she was referred to the
adverse cutaneous reaction that can follow para-arterial injections resulted in fine scarring.
endodontic department at Hamad Dental
intramuscular or intra-articular injections. This In contrast, the other 2 procedures caused
Center for assessment and completion of the
adverse reaction has been related to injections necrosis or even perforations. Based on this
root canal treatment.
of different drugs such as antibacterial agents, experiment, it can be speculated that the
In the endodontic department, all
bismuth, nonsteroidal anti-inflammatory drugs, injection of CH beyond the apex may cause
necessary clinical and radiographic
pethidine, vitamins, lidocaine chlorpromazine, serious damage to the tissue, especially when
examinations were performed (Fig. 2). A cone-
corticosteroids, and other drugs3,9,12–14. One in proximity to the vasculature. Perforation of
beam computed tomographic scan revealed
of the drugs that has been reported to cause the vessels due to overinstrumentation during
dislocation of some opaque material from the
NS is CH, which can initiate the same adverse endodontic treatment may further worsen the
canals of tooth 14 to the floor of the left
reaction as other drugs3. This reaction includes situation.
maxillary sinus, posterior superior alveolar
severe and immediate pain around the To date, there is no definitive treatment
artery, infraorbital artery, and the area of the
injection site, inflammation of the arteries, for NS. Depending on the extent of the
infraorbital foramen (Figs. 3 and 4). This
acute vasospasm followed by intense necrosis, the suggested treatments range from
material was likely the unset CH. The root canal
ischemia, and a hemorrhagic or livedoid topical medicaments, analgesics, antibiotics,
treatment was successfully completed over 3
reticular patch. Finally, the skin, subcutaneous systemic steroids, and anticoagulants to
visits. At the 6-month follow-up, a successful
outcome was indicated, and the patient’s pain
and soft tissue problems both resolved.

DISCUSSION
The reaction to inadvertent CH extrusion into
the soft tissue or blood vessels can vary from a
simple inflammatory reaction to serious
damage2,5,6,10. The first case report of the
adverse reaction to CH was published in
200011 and several more cases have been
reported since that time2,3,5,6.
In this case, the canals bled profusely
during the root canal therapy. Immediately
after the injection of CH, pain and ischemia in
the skin of the left cheek occurred. The
bleeding might be explained by the proximity of
the apices of the roots to the blood FIGURE 2 – The appearance of the skin when the patient attended the endodontic department at Hamad Dental Center.

270 Al-sheeb et al. JOE  Volume 48, Number 2, February 2022


FIGURE 3 – Three-dimensional construction of the cone-beam computed tomographic scan showing a contrast
material in the route of the infraorbital artery.
FIGURE 4 – A cone-beam computed tomographic image showing the presence of opaque material in the root of the
posterior superior alveolar artery.
surgical interventions4,9. This surgical
intervention may involve simple debridement in
mild cases or plastic surgery where the
destruction is greater. In this instance, the
extent of the patient’s tissue damage required
corrective plastic surgery.
JOE  Volume 48, Number 2, February 2022
The differential diagnosis of this case
could be a sodium hypochlorite accident.
Sodium hypochlorite and CH may cause
similar adverse reactions when extruded into
vital tissues. Both chemicals share similar
clinical features of severe pain, ecchymosis,
swelling, numbness, and necrosis12,16.
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1. ^ças IN, Magalh€aes FA, De Uzeda M. Antifungal effects of endodontic
Siqueira JF Jr, Rc
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2. Sharma S, Hackett R, Webb R, et al. Severe tissue necrosis following intra-arterial injection of
endodontic calcium hydroxide: a case series. Oral Surg Oral Med Oral Pathol Oral Radiol
2008;105:666–9.
Nicolau Syndrome after Endodontic Treatment
Moreover, sodium hypochlorite accidents can
progress to secondary infection, sinusitis, and
cellulitis. Although necrosis may or may not be
associated with sodium hypochlorite
accidents, it is considered a typical feature of
NS. The patient in the present case report
exhibited typical signs of NS, which include
immediate and severe pain after the injection of
the unset CH followed by skin erythema and
swelling. Finally, a necrotic skin patch at the
sight of the injection developed. Moreover, the
symptoms occurred directly after injecting the
root canals with the unset CH and not after
irrigation with sodium hypochlorite. The
radiopacities found in the cone-beam
computed tomographic scan, in the route of
several maxillary artery branches, also support
this theory.
NS is a preventable complication.
Injectable CH should be used with caution in
endodontic treatment. Careless handling of
injectable CH can easily result in its
displacement outside of the root canal
system, which may increase the likelihood of
the occurrence of NS. Blood vasculature
proximity to the apices of the roots is
another factor that increased the probability
of this syndrome. Clinicians should respect
the anatomic structure during root canal
therapy.
CONCLUSION
Despite the rarity of NS, it is important to
highlight the toxic effect of CH when displaced
beyond the apex. The main causes of CH
extrusion into the soft tissue, namely
overinstrumentation and forced injection,
especially when combined with profuse
bleeding from the root apex, should be
carefully avoided.
ACKNOWLEDGMENTS
The authors deny any conflicts of interest
related to this study. The authors received
financial support for the publication of this
article from the Oral Health Institute, Academic
Health System at Hamad Medical Corporation,
Doha, State of Qatar.
271
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13. Corazza M, Capozzi O, Virgili A. Five cases of livedo-like dermatitis (Nicolau’s syndrome) due to
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