What is C1 Esterase Inhibitor Deficiency?
Hereditary angioedema, also known as C1 esterase deficiency, is a condition that causes frequent swelling episodes (also known as “angioedema”) in the skin without the presence of hives or itching. Often, this swelling happens in the legs, hands, face, upper airways and gastrointestinal tract – the network of organs that help your body break down food. This condition is serious because it can lead to swelling in the airways, potentially resulting in suffocation due to the swelling of the voice box (larynx). Other symptoms can include stomach pain and vomiting, usually as a result of the condition affecting the digestive tract.
What Causes C1 Esterase Inhibitor Deficiency?
Hereditary angioedema is a condition that results from the overproduction of a substance called bradykinin. This substance causes the larynx, or “voice box” to expand and swell, which can be dangerous as it can block the airway. Unlike some types of swelling, this one does not respond to traditional medications – antihistamines – because it is not caused by the usual suspect, histamine.
Hereditary angioedema can occur in various forms, but the most common one involves an issue with a certain protein known as the C1 inhibitor. This protein usually helps regulate important biochemical pathways in the body. One of these pathways involves controlling bradykinin, which can cause angioedema if there’s too much of it.
It’s not entirely known what triggers the first steps leading to this swelling, although one widespread belief is that it involves a process linked to blood clotting known as the coagulation cascade. Generally, in this process, activated molecules called factor XII and kallikrein help turn another molecule called ‘kininogen’ into bradykinin. Essentially, the C1 inhibitor usually keeps the production of bradykinin in check by controlling kallikrein and factor XII.
Being a strong vasodilator, Bradykinin has a significant impact on the smooth muscles in our blood vessels, and this activity can cause surrounding tissues, and crucially, the airway, to swell. However, in people who don’t have enough of the C1 inhibitor, the production of bradykinin goes on uncontrolled, leading to considerable vessel expansion, or vasodilation, and angioedema.
Risk Factors and Frequency for C1 Esterase Inhibitor Deficiency
Hereditary angioedema is a condition that affects around 1 in 50,000 people. This illness is usually linked to about 300 harmful genetic changes, and most of these are inherited in a certain manner. It’s important to note that around a quarter of these cases start with new, spontaneous mutations. Due to this condition, there are around 15,000 to 30,000 emergency room visits each year.
Signs and Symptoms of C1 Esterase Inhibitor Deficiency
If you think someone might have C1 esterase deficiency, there are some things you should look for in their health history. This includes any family history of the disease, episodes of swelling in the upper airways, repeat episodes of severe stomach pain that goes away on its own, and sudden skin swelling without any signs of allergy or exposure to common triggers like ACE inhibitors, NSAIDs, or allergens. The hands and feet are usually the parts of the body that get affected.
- Family history of the disease
- Swelling in the upper airways
- Recurrent episodes of severe stomach pain that goes away on its own
- Sudden skin swelling without signs of allergy or exposure to common triggers
- Commonly affects hands and feet
Testing for C1 Esterase Inhibitor Deficiency
When a doctor suspects a person may have a deficiency in a special protein called C1 esterase inhibitor, they might notice that the person has difficulty breathing due to swelling in the voice box area, or they may just have unexplained swelling in their hands and feet. The first thing a doctor will do in this situation is make sure the person can breathe safely. This might be more difficult than usual because of the swelling in the throat.
The doctor may then try to reduce the swelling with treatments typically used for allergic reactions, such as epinephrine, steroids, and antihistamines. However, if the swelling is caused by a C1 esterase inhibitor protein deficiency, these treatments will not work.
At this point, the doctor might suspect that the person has a C1 esterase inhibitor deficiency, but to confirm this, the doctor will need to perform a blood test to check the level of a protein called C4 in the person’s blood. If the C4 levels are low, this supports the suspicion of a C1 esterase inhibitor deficiency.
The doctor can then perform further testing, such as checking the level and function of the C1NH protein in the person’s blood, to definitively diagnose a C1 esterase inhibitor deficiency.
Treatment Options for C1 Esterase Inhibitor Deficiency
If a person has a known condition involving a deficiency in C1 esterase inhibitor – an enzyme in the body – and they’re experiencing mild symptoms, doctors usually monitor the patient’s condition without interfering. However, if the situation worsens and the patient experiences severe symptoms such as difficulty breathing due to swelling near the throat, a medical intervention is needed to secure the patient’s airway. To manage this situation, doctors often administer treatments like epinephrine, steroids, and antihistamines.
While these medications are typically effective in treating swelling in the throat caused by allergies, they may not always work for people with C1 esterase inhibitor deficiency. However, doctors usually try these treatments because they’re generally safe with potentially huge benefits to the patient. The most effective therapy for people with C1 esterase inhibitor deficiency experiencing throat swelling is to provide them with additional C1 esterase inhibitor.
This can be given in the form of human plasma, a part of blood that carries this enzyme. Another way to provide the deficient enzyme is to use a concentrate of C1INH (another name for this enzyme) derived from human plasma. There are also several specific and less commonly used medications for treating throat swelling due to this enzyme deficiency. These include Icatibant, a man-made drug that works against a protein called bradykinin that causes inflammation, and Ecallantide, a drug that blocks a plasma protein known as kallikrein, which plays a role in inflammation.
What else can C1 Esterase Inhibitor Deficiency be?
If a person is suffering from airway swelling, there could be multiple causes for this. Doctors need to consider various potential diagnoses such as:
- An extreme allergic reaction
- Swelling caused by certain blood pressure medications (ACE inhibitors)
- Swelling that has no identifiable cause (idiopathic)
- Autoimmune disorders where the body’s immune system attacks its own tissues
- Superior vena cava syndrome which is a blockage of blood flow in a large vein near the heart
- Disorders associated with the thyroid, a gland in the neck
- Cheilitis granulomatosa, a rarely seen disorder that causes persistent lip swelling
- Trichinosis, an infection caused by roundworms typically from eating undercooked, infected meat
Doctors then analyze the swelling of the limbs in order to make the diagnosis more comprehensive. Below are different conditions that could be causing this:
- Lymphedema, a condition which causes swelling in the arms and legs due to a blockage in the lymphatic system
- Deep vein thrombosis, a blood clot in a deep vein, often in your legs
- Cellulitis, a common bacterial skin infection
What to expect with C1 Esterase Inhibitor Deficiency
Typically, patients should return to good health depending on how they respond to treatment. However, in some rare cases, patients may not react well to the therapy and may need a procedure called intubation. Intubation involves inserting a tube through the mouth and then into the airway so you can breathe.
After the critical phase and removing the tube (a process called extubation), patients should be on the path to complete recovery. However, it’s important to keep in mind that there’s always a possibility of the condition coming back.
Possible Complications When Diagnosed with C1 Esterase Inhibitor Deficiency
The most serious complication that can occur is when the patient’s airway becomes blocked. This may require the insertion of a tube, or even surgery, to clear the airway. However, health professionals can generally manage this using standard airway procedures and protocols.
Common Side Effect:
- Airway becoming blocked requiring tube insertion or surgical intervention.
Preventing C1 Esterase Inhibitor Deficiency
It’s essential to stay away from things that cause physical and mental stress. It’s also important to avoid taking certain medications, such as estrogen, tamoxifen, and ACE inhibitors. These could potentially harm your health.
If you’re scheduled for dental surgery, your doctor will give you a special treatment to prepare your body. This treatment will likely include milder forms of male hormones, regular infusions of a compound called C1INH, and an infusion of a medicine called tranexamic acid. These treatments help to manage your body’s response to the surgery, ensuring you are as healthy as possible for the procedure.
