Table of Contents
What Is Nicolau Syndrome?
Nicolau syndrome (NS), or embolia cutis medicamentosa or livedoid dermatitis, is a rare skin reaction after getting injections in muscles or joints with certain medications. This condition is named after Spanish dermatologists Freudenthal and Nicolau, who first described it in 1925. It was first noticed when someone got an injection of bismuth for syphilis in their gluteal region. Nicolau syndrome must be better understood due to its rarity and varied clinical presentations. The typical signs of this syndrome include pain right after the injection, followed by redness, a patchy appearance on the skin, and sometimes bleeding. NS can cause the skin, fat, and muscle layers to necrose. Different kinds of drugs can trigger it.
What Causes Nicolau Syndrome?
The exact cause of Nicolau syndrome is unclear, but it is believed to start with problems with blood vessels. It is thought that the main reasons are the sudden narrowing of blood vessels, inflammation of arteries, and blockages in small arteries (called arterioles). This can lead to intense pain because it leaks around the arteries and nerves.
Also, the body's response to this, including nerve signals and further narrowing of blood vessels, can cause the skin not to get enough blood and eventually die (necrosis). Sometimes, when medicines are accidentally injected into blood vessels, they can cause inflammation or blockages in the arteries, leading to skin damage.
Various medications have been implicated in triggering Nicolau syndrome, including nonsteroidal anti-inflammatory drugs (NSAIDs), corticosteroids, antibiotics, vaccines, and local anesthetics. Nicolau syndrome due to diclofenac injection is the most reported. Diclofenac, a common pain reliever, can cause blood vessels to narrow, which might explain why it can trigger Nicolau syndrome.
The Risk Factors for Developing Nicolau Syndrome Include:
-
Improper injection technique.
-
The use of large bore needles.
-
Repeated injections at the same site.
-
Pre-existing vascular diseases.
What Are the Symptoms and Stages of Nicolau Syndrome?
The symptoms of Nicolau syndrome are differentiated into three stages or phases based on the condition's progression.
Initial Phase:
In this phase, patients experience intense pain shortly after receiving the injection. Some may also feel pain radiating to other parts of the body, and in some cases, there could be neurological symptoms like peroneal neuropathy. Faintness or even fainting might occur. Initially, the injection site may appear bluish, followed by redness or hemorrhagic lesions. Eventually, skin, soft tissue, and even muscles can show signs of damage.
Acute Phase:
The acute phase of Nicolau syndrome typically occurs within 24 hours to 3 days after the injection. During this phase, the skin at the injection site may become red and swollen. Sometimes, there can be painful patches with a border that looks purplish or net-like. These patches usually do not show signs of skin death yet.
Necrotic Phase:
In the final stage, known as the necrotic phase, the skin at the injection site progresses to a dark, necrotic (dead) state, often crusty. The region might also swell up and feel sore. This phase usually occurs around five days to two weeks after the injection. Patients may experience pain, and the skin might develop black areas, indicating tissue death. In severe cases, large patches of skin may ulcerate, exposing the underlying tissue.
Nicolau syndrome most commonly affects the buttocks, but it can also occur in other areas, such as the shoulder, thigh, knee, ankle, breast, and abdomen. In complicated cases, extensive skin necrosis, changes in blood supply to the affected limb, and even neurological problems can occur.
How Is Nicolau Syndrome Diagnosed?
The diagnosis of Nicolau syndrome is made through clinical evaluation, including a detailed history of recent injections and a physical examination of the skin. Other investigations that may be done are
Laboratory Tests - Blood tests usually show no significant abnormalities initially. However, markers of muscle damage like creatine kinase, myoglobin, and certain liver enzymes may be elevated. Sometimes, there can be an increase in white blood cell count and inflammatory markers.
Imaging Studies - Ultrasound may not show abscesses but can reveal muscle swelling. Computed tomography (CT) scans may show inflammation in the fatty tissue but usually do not involve the muscles. Magnetic resonance imaging (MRI) may show fluid collection and muscle changes, particularly in later stages.
Biopsy - Skin biopsy is often performed to confirm the diagnosis, revealing histopathological features consistent with ischemic necrosis, dermal thrombosis, and inflammatory infiltrates. Tissue samples taken during surgery show signs of fat tissue damage and inflammation. Cultures - Tests for bacteria, fungi, and mycobacteria are usually negative or show only normal bacteria.
Differential Diagnosis:
Initially, Nicolau syndrome may be mistaken for a local drug reaction or bleeding. Other conditions, like compartment syndrome or heart problems, must be ruled out. It is essential to differentiate between conditions like vasculitis and fat embolism. Sometimes, it is misdiagnosed as cellulitis, leading to incorrect antibiotic treatment. If there is a suspicion of cancer, a biopsy may be done.
How Is Nicolau Syndrome Treated?
Treatment of Nicolau syndrome involves addressing its different phases, ranging from medication to surgery, depending on the severity of the condition.
Initial Phase
-
The focus is on managing severe pain with painkillers and dressing the affected area.
-
It is necessary to rule out other conditions that may mimic NS.
-
Ice packs should be avoided, as they can worsen blood vessel spasms.
-
If there is suspicion of infection, antibiotics may be prescribed until infection is ruled out.
Acute Phase
-
Medications like steroids and blood thinners are commonly used to reduce inflammation and prevent blood clots.
-
Hyperbaric oxygen therapy may also be considered.
-
Warm compresses can help improve symptoms.
Necrotic Phase
-
Surgical removal of the affected tissue is necessary if the skin and tissues show necrosis.
-
After removing the damaged tissue, skin grafts or reconstructive surgery may help heal the wound.
-
In most cases, the wound heals well, although scarring may occur.
Can Nicolau Syndrome Be Prevented?
The right injection method should be used, and the rules for giving medicine should be followed to avoid Nicolau syndrome. To make sure drugs are injected safely, it is important to confirm that they do not leak out of blood vessels. This is done by pulling back the syringe plunger to check for blood before giving the injection. For intramuscular injections, choosing the upper outer part of the buttocks, where there are fewer blood vessels, is best to minimize the risk of leakage.
Conclusion
Nicolau syndrome is a rare but serious problem that can happen at the injection site. It causes skin necrosis because the blood vessels get blocked, and the area does not get enough blood. Although the cause is unknown, different medications and injections may play a part in causing it. It is important to quickly recognize and treat problems to avoid more issues and help the patient improve.
