What Is Hereditary Angioedema?
Hereditary angioedema is a rare genetic condition that causes recurrent swelling in limbs, face, intestinal tract, and airway. This disorder causes swelling under the skin and at the lining of the guts and lungs. Usually, there are no known triggers that aggravate this condition. However, minor trauma seems to be an aggravating factor for swelling in some cases. It is an autosomal recessive condition caused by either lack of C1 inhibitor protein or a dysfunctional inhibitor protein. Hereditary angioedema is a rare condition affecting 1 in 50,000 people, among which type III is the rarest compared to the other two types. The condition is also known as
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C1 esterase inhibitor deficiency.
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C1 inhibitor deficiency.
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HAE.
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HANE.
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Hereditary angioneurotic edema.
What Are the Types of Hereditary Angioedema?
The types of hereditary angioedema are classified as
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Type I: Type I hereditary angioedema accounts for almost 85 % of the cases. Low C1 inhibitor levels in the blood cause this type of disorder.
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Type II: Type II hereditary angioedema accounts for almost 15 % of all cases. This type of disorder occurs due to improper protein functioning in the body. However, the C1 inhibitor level is normal or close to normal in the body.
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Type III: Type III hereditary angioedema is the rarest variant of the disorder. However, it is very similar to the other two types.
What Are the Causes of Hereditary Angioedema?
The following are the etiological factors associated with hereditary angioedema:
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Type I and Type II: SERPING 1 gene mutation is responsible for the occurrence of type I and type II hereditary angioedema. This gene works as an instructor for making C1 inhibitor protein. This protein is responsible for controlling the inflammatory response of the body. Type I causes a low level of this inhibitor, whereas type II causes an abnormal level. Without the normal level of this inhibitor, the protein fragment called bradykinin is generated. This accelerates the fluid leakage through the blood vessel walls in the tissue and promotes the inflammation reaction in the body.
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Type III: F12 gene mutation is associated with type III hereditary angioedema. This gene acts as an instructor in making the coagulation factor XII protein. Coagulation factor XII plays an essential role in the blood clotting mechanism and the production of bradykinin. Bradykinin is a peptide that promotes inflammation. With the genetic mutation in F12, the coagulation factor production increases, which leads to increased bradykinin production. This results in leaky blood vessels and gives rise to inflammatory episodes in the body.
What Are the Signs and Symptoms of Pregnancy and Hereditary Angioedema?
The symptoms of hereditary angioedema show its first sign during childhood or puberty and persistently recur throughout life. The followings are the signs and symptoms associated with hereditary angioedema:
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Nausea.
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Pain.
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Nonpruritic wavy rash.
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Vomiting.
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Diarrhea.
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Extreme fatigue.
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Muscle ache.
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Tingling.
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Belly pain.
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Hoarseness.
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Mood swing.
What Are the Triggers of Hereditary Angioedema?
The following are the common triggers that cause hereditary angioedema:
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Stress or anxiety.
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Minor injury.
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Surgery.
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Cold or flu.
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Continuous physical activities such as typing, hammering, or gardening.
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Continuous use of medication for heart conditions.
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Periods.
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Pregnancy.
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Use of birth control.
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Hormone replacement therapy.
How to Diagnose Hereditary Angioedema?
If the episodes of swelling are nonresponsive to the drug treatment, doctors may recommend diagnostic options. If the swelling occurs without any rashes or known triggers to the body, doctors may recommend the following diagnostic options:
History:
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As the disorder is hereditary, doctors start by asking about family history. Almost 75 % of the cases show a positive family history of this condition.
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some psychological triggers aggravate the condition, such as stress, and anxiety. Besides these, triggers such as infection or allergies also cause this condition.
Examination:
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Physical examination of the swellings can also help with the diagnosis.
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The condition represents airway swelling; the doctors usually look for swelling in the tongue, soft palate, or uvula.
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Doctors also check for any laryngeal alteration, such as hoarseness or stridor.
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The condition represents swelling of limbs or face; this can be one of the many factors doctors check for.
Investigation:
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Measurement of the Components - Levels of C4, C1 inhibitor, and C1q are measured.
Complement Levels in Hereditary Angioedema, Acquired Angioedema, and ACE Inhibitor–Induced Angioedema
What Is the Differential Diagnosis of Hereditary Angioedema?
The following are the differential diagnoses associated with hereditary angioedema:
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ACE inhibitor-induced angioedema.
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Acquired angioedema syndrome.
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Immediate hypersensitivity reactions.
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Urticaria.
How Is Hereditary Angioedema Managed?
Resuscitation:
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In case of an emergency when a person is unable to breathe, immediately seek medical attention.
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After careful diagnosis, the doctor may give intravenous C1-INH 20 units/kg over ten minutes.
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The doctor might have to go for emergency intubation or a cricothyrotomy.
Initial Management: If an allergy is diagnosed, doctors might refer the case to an immunologist.
Further Management:
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Facial and Airway Swelling:
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Upper airway involvement progresses slowly within 20 minutes after the first symptoms appear.
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In any case of airway involvement, doctors usually recommend C1-INH promptly.
Abdominal Pain and Vomiting:
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In case of abdominal pain, NSAIDs are given.
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In case of vomiting, severe pain in the abdomen, or abdominal distention, doctors may go for C1-INH administration.
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If the symptoms do not improve and last longer than two hours, doctors take a second dose of C1-INH administration along with opiate analgesia and intravenous fluids.
Limb Involvement:
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Mild swelling usually subsides on its own within a few days.
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However, for severe cases, doctors may recommend the hospitalization and administration of C1-INH.
Medications:
Long-Term Prophylaxis:
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Plasma-derived C1 inhibitor.
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Lanadelumab.
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Berotralstat.
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Attenuated androgens.
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Antifibrinolytics.
Short-Term Prophylaxis:
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Human nano-filtered purified C1 inhibitor 1000 units intravenous one to two hours before the procedure.
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200 mg of Danazol three times a day.
Follow-up:
Every treatment needs to be followed up, especially if the condition is severe and the treatment was prolonged due to its severity. In this case, the patients should go for regular follow-ups as recommended by doctors.
Conclusion
Hereditary angioedema is a very rare condition. However, the condition might often be neglected due to its common symptoms. The mild symptoms might go away on their own, but in the case of severe signs such as difficulty breathing, the patient should be rushed to the hospital. Moreover, once the treatment is over, the patient should go for a regular follow-up to avoid the recurrence of this condition.