Signs and Symptoms - Swelling of the face, tongue, larynx, abdomen, or arms and legs - Associated with hives or urticaria - Onset typically over minutes to hours - May cause itching or pain - Severe cases can lead to respiratory distress and require intubation

Causes and Triggers - Allergic reaction to agents such as insect bites, foods, or medications - C1 esterase inhibitor deficiency, angiotensin-converting enzyme inhibitors, or lymphoproliferative disorder - Idiopathic or weakly correlated to allergen exposure - Hereditary angioedema often has no identifiable cause - Triggers can include infections, minor injuries, mechanical irritation, operations, or stress

Pathophysiology - Histamine or bradykinin are involved in the underlying mechanisms - Histamine-related angioedema is allergic in nature - Bradykinin-related angioedema is caused by C1 esterase inhibitor deficiency or medication - Bradykinin is a potent vasodilator and increases vascular permeability - ACE inhibitors block the degradation of bradykinin

Diagnosis - Clinical picture and medical history are important for diagnosis - Routine blood tests are performed to assess overall health - Mast cell tryptase levels may be elevated in allergic reactions - Complement levels, especially depletion of complement factors 2 and 4, may indicate C1-inhibitor deficiency - HAE type III is diagnosed by excluding other causes and observing angioedema with normal C1 levels and function

Treatment - Protection of the airway may require intubation or cricothyroidotomy - Antihistamines, corticosteroids, and epinephrine can be used for histamine-related angioedema - C1 esterase inhibitor, ecallantide, or icatibant may be used for bradykinin-related angioedema - Fresh frozen plasma can also be used as a treatment - Treatment should be tailored to the underlying cause and severity of the angioedema

Acquired Angioedema - Can be immunologic, nonimmunologic, or idiopathic - Usually caused by allergy and occurs with other allergic symptoms and urticaria - Can be a side effect of certain medications, especially ACE inhibitors - Characterised by repetitive episodes of swelling in various body parts - Edema of the gastrointestinal mucosa can cause severe abdominal pain and in the upper respiratory tract, it can be life-threatening

Hereditary Angioedema - Exists in three forms caused by genetic mutations - Types I and II caused by mutations in the SERPING1 gene - Type III linked with mutations in the F12 gene - All forms lead to abnormal activation of the complement system - Can cause swelling in various parts of the body, including the digestive tract and larynx, which can be life-threatening

Management - Allergic angioedema can be prevented with avoidance of allergens and antihistamines - Severe cases may require desensitization or steroid therapy - Drug-induced angioedema caused by ACE inhibitors should be treated by discontinuing the drug and finding an alternative treatment - Hereditary angioedema does not respond to antihistamines, corticosteroids, or epinephrine - Acute treatment for hereditary angioedema includes C1-INH concentrate or fresh frozen blood plasma

Acquired Angioedema Treatment - Antifibrinolytics such as tranexamic acid or ε-aminocaproic acid may be effective - Cinnarizine can be useful in patients with liver disease - Androgens like danazol, oxandrolone, or methyltestosterone can prevent future attacks of HAE - Lanadelumab, an injectable monoclonal antibody, can prevent attacks of HAE types I and II - Icatibant and ecallantide are medications that may be used to treat attacks of hereditary angioedema

Epidemiology - In the U.S., there are 80,000 to 112,000 emergency department visits for angioedema annually - Angioedema ranks as the top allergic disorder resulting in hospitalization - The exact prevalence of angioedema is unknown - Acquired angioedema is more common than hereditary angioedema - Hereditary angioedema affects approximately 1 in 50,000 people

Complications and Prevention of Angioedema - Potential airway obstruction leading to respiratory distress or asphyxiation - Recurrent episodes of angioedema can significantly impact quality of life - Prevention strategies include avoiding known triggers and allergens - Genetic counseling and testing for individuals with hereditary angioedema - Education and awareness about angioedema and its potential complications