Types |
| Hereditary angioedema type I, II, III Acquired angioedema Drug-induced angioedema Angioedema with urticaria Angioedema without urticarial Idiopathic angioedema |
Introduction |
| Angioedema is a swelling that occurs in the tissues deep below the surface of the skin involving the dermis, subcutaneous tissue, mucosa and submucosa. It occurs rapidly in the face, eyes, lips, throat and are similar to hives . It should be treated as a medical emergency. |
Causes |
| Most common form (90%) of angioedema is with urticaria and is a hypersensitivity due to an offending agent. The pathophysiology in this setting starts with the offending allergen binding to the endothelial cell in our veins/arteries. The body’s immune system gets activated upon detecting a foreign body. Histamine is released inducing an increase in vascular permeability within the cells. Once this process is started, in severe situations additional protein degrading peptides may activate the complement system in our body, specifically, C3a, C4a and C5a, which work with our immune system. The resultant manifestation is severe edema, generalized urticaria and anaphylaxis. Mortality is therefore related to the severity of airway obstruction. Asphyxiation due to laryngeal edema yields a 3-40% mortality rate. Reported causes of angioedema with urticarial includes: Animal dander, exposure to water, exposure to extreme temperatures (heat, cold), Foods (including berries, shellfish, nuts, egg, milk), insect bites, medications (sulfa, penicillins, NSAIDs, ACE-Inhibitors), pollen, autoimmune diseases and systemic infections.Although most forms of angioedema are considered to be of unknown etiology (offending agent cannot be found), 10% of angioedema occurs without urticaria and is considered to be kinin-mediated rather than a hypersensitivity reaction. Examples of the kinin-mediated subtypes include hereditary angioedema and acquired angioedema. They are generally due to dysfunctional or insufficient C1 esterase inhibitors. C1 esterase is an inhibitory protein that is found in the fluid part of your blood. It controls the first component of your body’s complement system, C1. A group of proteins that move freely in your bloodstream and work with your immune system is known as the complement system. It plays a major role in the development (or blockade) of inflammation in your body. There are nine major complement proteins in the system, C1 to C9, each with a separate and significant role. C1 esterase is involved in the (inhibitory) regulation of bradykinin, a potent vasoactive substance. By keeping the bradykinin supressed, the body avoids induction of inflammation/edema, vasodilation, modulates growth factors and unnecessary proliferation/contraction of endothelial and smooth muscle cells.
However, a deficiency or dysfunction of the first component, C1 esterase, results in elevated levels of bradykinin in the blood. This causes inevitable activation of a fibrinolytic molecular cascade with increased circulation of vasoactive substances and increased vascular permeability manifesting as edema and inflammation. In this setting, several causative factors can trigger a spontaneous episode. Exposure to stress, allergens, certain medications (i.e. ACE inhibitors (frequency of 0.1-0.7%)), are some reported exacerbating factors. Hereditary angioedema has been associated with defective gene that regulates production of C1 esterase inhibitor. Acquired angioedema is associated with autoantibodies that attack this protein, inducing dysfunction. |
Symptoms |
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Physical Examination |
On examination by a physician the following may be identifiable:
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Differential |
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Diagnosis |
| Diagnosis of IgE-mediated angioedema usually is made on the basis of the clinical presentation; however, skin testing or radioallergosorbent tests for foods may be confirmatory.Hereditary angioedema is characterized by low levels of C1 esterase inhibitor (C1-INH) or elevated levels of dysfunctional C1 esterase inhibitor, as detected by an immune assay. Between attacks, low levels of C4 are noted. |
Treatment & Management |
Mild symptoms may not need treatment as they are usually self-limiting, resolving within hours to days.Moderate symptoms may need treatment.
Difficulty in breathing warrants emergency treatment.
Hereditary angioedema is generally refractory to the use of catecholamines, antihistamines, and steroids. Anabolic steroids, such as danazol, may be used for the acute phase of an attack of hereditary angioedema. C1 esterase inhibitor (approved for acute HAE in September 2009) may also be infused as short-term treatment, though this drug is also used for prophylaxis in recurrent cases. In December 2009, ecallantide (Kalbitor) was approved by the FDA for treating acute HAE attacks. During attacks, unregulated plasma kallikrein activity results in excessive bradykinin generation, resulting in swelling, inflammation, and pain. Ecallantide is a potent, selective, reversible inhibitor of plasma kallikrein, thereby reducing the conversion of kininogen to bradykinin. |
Expected Management |
Once the patient is in the emergency room, your physician may order:
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Complications |
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–Reviwed by: Nina Jaitly, MD, Medical Editor, Living Healthy World Wide.com