Also known as Embolia Cutis Medicamentosa (ECM)
and Livedo-Like Dermatitis (LLD).
It was firstly reported by Freudenthal and Nicolau in
1924 and 1925, respectively, following the intramuscular
injections of bismuth to treat syphilis.
WHAT IS NICOLAU SYNDROME?
Nicolau syndrome is an uncommon iatrogenic ischemic necrosis of the skin and deeper tissue. Although it is quite rare, it as been
reported to occur after intramuscular injections of different medications, especially diclofenac, penicillin,
non-steroidal anti-inflammatory drugs (NSAIDs), topical
anesthetics (lidocaine), vaccines, corticosteroids, vitamin
One of the drugs that has been reported to cause Nicolau syndrome is Calcium Hydroxide used as an intra canal medicament in endodontics, which can initiate the same adverse reaction as other drugs.
Some studies have related it to subcutaneous, intravenous and intra-articular injections of some drugs.
However, intra/periarterial injections and their consequent complications such as ischemia and spasms are
known as the possible contributing factors.
NICOLAU SYNDROME AFTER ENDODONTIC TREATMENT:The first case of the adverse reaction to intra canal medicament Calcium Hydroxide was published in 2000 and several more cases have been reported since that time.The reaction to inadvertent Calcium Hydroxide extrusion into the soft tissue or blood vessels can vary from a simple inflammatory reaction to serious damage.
In some cases where the canals bleed profusely during the root canal therapy, the bleeding might be explained by the proximity of the apices of the roots to the vascular structure. Immediately after the injection of intra canal Calcium Hydroxide, pain and ischemia in the skin extraorally occurr.
It can be hypothesized that the extrusion of the Calcium Hydroxide may cause direct trauma to the vascular structures. Inflammation of the arteries and arterial embolism due to crystallization of the drug occurrs, leading in turn to ischemia and local necrosis. These clinical features are described as Nicolau syndrome.
Calcium Hydroxide displaced beyond the apex
Despite the rarity of Nicolau syndrome, it is important to highlight the toxic effect of Calcium Hydroxide when displaced beyond the apex. The main causes of Calcium Hydroxide extrusion into the soft tissue, namely overinstrumentation and forced injection, especially when combined with profuse bleeding from the root apex, should be carefully avoided.
ETIOLOGY OF NICOLAU SYNDROME-
The etiology of this syndrome is not well-known yet, so
microscopic and biopsy studies suggests ischemic tissue
necrosis which may be due to inadvertent intra/peri-arterial injection, leading to embolism and vascular occlusion or may be due to vasospasm due to the needle prick of the injected drug; and applying a cold compress to the lesion site.
It is most probable that a combination consisting of
vasospasm, thrombosis, and embolism mechanisms is
involved in developing the final lesion.
SYMPTOMS OF NICOLAU SYNDROME-
In general, at onset 90% of the affected cases was accompanied with severe pain during injection.
After several hours, this may be followed by discoloration of the affected area, and ulceration in the injection site.
After several days, about 55% of the cases developed necrosis in the affected area and necessitated debridement.
Given that Nicolau syndrome can occasionally be hazardous, with irreparable consequences and may even cause death.
There is no confirmatory test for Nicolau syndrome; therefore, its diagnosis is often performed based on patients’ medication history and clinical symptoms.
u The most frequent treatments performed in the reviewed cases were pharmacotherapy and debridement of necrotic tissue.
u Pharmacotherapy was mainly applied through systemic antibiotics, anticoagulants, systemic corticosteroids, antibiotics, topical corticosteroids, and various analgesics, including NSAIDs and opioids
u Generally, in most of the cases, therapy was started by symptomatic treatment of pain, bruising, swelling, and inflammation of the injection site.
u In symptoms exacerbation or necrotic lesions, some measures such as fasciotomy, necrotic tissue debridement, and plastic surgery (even amputation in case of extensive necrosis) may e required.
The effective factors on preventing Nicolau syndrome:
ü Ensuring drug’s safety.
ü Checking expiration date and using an appropriate solvent.
ü Ensuring proper drug’s preparation.
ü Preparing entirely uniformed and clot-free suspension.
ü Choosing the right size needle.
ü Ensuring that the needle is long enough to prevent the injection into adipose tissue, but to reach the muscle, especially in the buttock area.
ü Selecting the correct injection site, as in the upper-outer quadrant.
ü Ensuring the precise amount of injection.
ü Maximum 5 mL in each injection site.
ü Ensuring the usage of the correct injection techniques.
ü Syringe aspiration before injection.
ü Rotation of injection site if multiple injections are required at once using the Z-track technique.