Angioedema is swelling in the skin and submucosal tissues caused by blood vessel dilation and leakage. The condition can be divided into allergic angioedema which is triggered by allergens such as insect bites or drugs like pencillin. Hereditary angioedema where a person has inherited a rare genetic disorder due to deficiency of C esterase inhibitor (C1-INH) protein that controls inflammatory reaction. Acquired angioedema is associated with autoimmune disease like systemic lupus erythematosus (SLE), or idiopathic thrombocytopenic purpura (ITP), and with chronic use of angiotensin-converting enzyme inhibitors. These kinds of angioedemas can cause accumulation of fluid and swelling in specific body areas. 

Allergic angioedema is a rare condition that affects 0.1% to 20% of the population and is more common in children and young adults. Hereditary angioedema (HAE) affects one in 10,000 to one in 50,000 people and can affect individuals of any age, gender, or ethnicity. Acquired angioedema, a rare form, is more common in adults and can be associated with underlying medical conditions like autoimmune disorders or malignancies. The exact prevalence of these conditions is not well established. 

This is referred to a condition that is categorized into two types that is histamine- mediated and bradykinin-mediated. The former is more common and is caused by mast cells as well as basophils while the latter includes hereditary angioedema, acquired C1- inhibitor deficiency and angiotensin-converting enzyme (ACE) inhibitor– associated angioedema. In bradykinin-mediated angioedema, there is excessive production of kallikrein which is not regulated leading to breakdown of high molecular weight kininogen into bradykinin thereby increasing vascular permeability and causing edema. NSAID- induced angioedema can occur through this mechanism too if it results from C1 inhibitor deficiency or ACE inhibitor– associated angioedema. Mutations in the F12 gene may cause hereditary angioedema while those within angiopoietin-1, plasminogen or other unidentified genes could also get involved. Deficiency of C1 inhibitor is associated with mutations in SERPING gene or any other genes encoding enzymes that metabolize and function in bradykinin pathway.  

Hereditary angioedema (inherited) results from mutations in the gene that encodes C1-inhibitor and is inherited in an autosomal dominant manner. Acquired cases are due to infection and drug induced lymphoproliferative disorders, neoplastic diseases, and autoimmune diseases. 

Histaminergic angioedema is an uncommon disease tat starts shortly after the exposure to an allergen and may persist for up to two days. It is frequently misdiagnosed or diagnosed very lately due to elements like absence of family history as well as involvement of the gastrointestinal tract rather than the skin. Attacks are usually more severe in type 1 and type 2 C1 inhibitor deficiency related angioedema. 

Angioedema can be acute or chronic and varies by type. Histaminergic angioedema affects multiple systems, including skin, respiratory, and gastrointestinal systems. It begins within 60 minutes of allergen exposure and lasts for one to two days. Causes include drugs, foods, latex, and insect stings. Bradykinin-mediated angioedema is more severe and longer-lasting, often involving abdominal symptoms. Acquired angioedema related to ACE inhibitors presents without urticaria or itching, common in African-Americans. NSAID-induced angioedema has urticaria and facial swelling. Hereditary angioedema starts in childhood or young adulthood and worsens at puberty. Symptoms include recurrent swelling or abdominal pain, prodromal symptoms, and acute attacks. Acquired angioedema with C1 inhibitor deficiency presents similar to hereditary angioedema, often due to an underlying lymphoproliferative disorder increasing protein consumption and producing an antibody against C1-INH, causing bradykinin overproduction. 

A physical examination for angioedema involves several key components. These include an inspection of the affected areas for visible swelling, color changes, palpation of the skin texture, and temperature changes. If the swelling affects the face, lips, tongue, or throat, the airway should be evaluated for any signs of compromise or difficulty breathing. Movement and function should be assessed for any limitations in movement or functional impairment caused by the swelling. Associated symptoms include pain or discomfort, and sensations of itching or tingling in the affected areas. These examinations help identify any signs of angioedema and its associated symptoms. 

1. Death from asphyxiation 
2. Acute laryngeal, tongue and pharynx swelling 
3. Critical airway occlusion leading to death 
4. Pancreatitis 
5. Cardiovascular instability 

Angioedema treatment varies based on the underlying cause and symptom severity. Allergic angioedema can be treated with non-sedating antihistamines, oral or topical corticosteroids, or epinephrine injections. Hereditary angioedema (HAE) can be treated with acute attacks using medications targeting the bradykinin pathway. Long-term prophylactic treatment may be needed for frequent or severe attacks. Identifying and avoiding triggers can help prevent HAE attacks. Acquired angioedema involves addressing the underlying condition, such as immunosuppressive therapy or discontinuing offending medications. Supportive care, such as antihistamines or corticosteroids, can help alleviate symptoms. Symptomatic treatment includes ensuring a patent airway and appropriate oxygenation, providing pain relief with analgesics, and educating patients about triggers, avoidance strategies, and early recognition of symptoms for prompt management. 

Allergy and Immunology

Angioedema can be managed through various strategies, including cold compresses, avoiding triggers, patient education, airway management, and psychological support. Cold compresses can reduce swelling and provide relief. Identifying triggers and avoiding them can prevent episodes. Patient education helps patients recognize symptoms, understand triggers, and emergency management steps. If angioedema affects the airway, immediate medical attention is needed. Psychological support, counseling, and stress management techniques can help individuals cope with the condition. 

Allergy and Immunology

Epinephrine: It is used in the treating laryngeal edema. It increases the peripheral vascular resistance and lowers vascular permeability. 

Allergy and Immunology

Diphenhydramine: It is indicated to relieve the symptoms due to histamine release. 

Chlorpheniramine: This is a first generation drug that competes with H1-histamine receptor sites on effector cells in the blood vessels. 

Cyproheptadine: It is used as a symptomatic relief in treating allergies due to release of histamine. 

Allergy and Immunology

Fexofenadine: It is a non-sedating antiallergic drug which is well tolerated. 

Cetrizine:  It selectively inhibits H1 histamine receptors in the GI tract, respiratory tract and blood vessels.  

Desloratidine: It is a long-acting histamine antagonist which is specific to H1 receptor. 

Allergy and Immunology

Cimetidine: It is a nonprescription antihistamine H2-receptor antagonist which can increase the serum level of hydroxyzine. 

Ranitidine:  It is a nonprescription antihistamine H2-receptor antagonist with better safety profile, strong binding to H2-receptor and will not suppress cytochrome P450 isozymes. 

Allergy and Immunology

Montelukast: This blocks the binding of leukotriene D4 to the receptor. It is used to treat urticaria. 

Zafirlukast: It is a competitive antagonist of leukotrienes D4, E4 and C4. 

Allergy and Immunology

Doxepin: It is tricyclic antidepressant which has potent blocking activity against H1 receptor. 

Allergy and Immunology

Prednisone: This drug can bring down the body´s reaction to various harmful triggers by decreasing the capillary permeability and inhibiting the activity of PMN, as these functions are responsible for increased inflammation which typically occurs in response to certain physiological or pathological processes. For it to become effective, prednisone must transform into prednisolone, which is an active metabolite. However, its conversion process might be interfered with when one is suffering from complications related to the liver.  

Prednisolone: It is available as oral formulations which decreases vascular permeability. 

Methylprednisolone: It is available an intravenous formulation to reduce vascular permeability. 

Allergy and Immunology

Danazol: It increases the levels of C1-INH and C4 and lowers the attacks due to angioedema. 

Allergy and Immunology

Oxandrolone: This is a synthetic derivative of androgen which can be used in pediatric population primarily in the prophylaxis of HAE. 

Allergy and Immunology

Aminocaproic acid: It is known to inhibit the process of fibrinolysis via inhibition of plasminogen activating g factors through antiplasmin activity. 

Tranexamic acid: It is used as an alternative aminocaproic acid. It also inhibits fibrinolysis through displacement of plasminogen from fibrin. 

Allergy and Immunology

Ecallantide: It is a selective, potent, and reversible inhibitor of plasma kallikrein. It is indicated to treat acute, episodic attacks of HAE via binding to the plasm akallikrien and blocking the binding site. 

Icatibant: The purpose of icatibant is to stop bradykinin from binding the B2 receptor and thus provide a cure for edema blockage.  

Allergy and Immunology

Omalizumab: It is indicated in treating angioedema in patients who are irresponsive to high doses of treatment with antihistamines. 

Allergy and Immunology

Patient education in hereditary angioedema is about personal education, planning and scheduling strategies, and aseptic technique. Parents/ guardians should be trained on C1-inhibitor injection site, needle preparation, and injection. During the first few months it is important for there to be follow-up care with patients who should keep a logbook to maintain treatment compliance that includes a description of breakthrough attacks.