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HAE-C1INH is the best-known type of hereditary (i.e. familial) angioedema. HAE-C1INH results from mutations in the gene encoding C1 inhibitor, resulting in low levels of active C1 inhibitor in the blood. In almost all instances, patients are heterozygous, meaning that they have 1 normal C1 inhibitor gene and 1 mutated C1 inhibitor gene. Two subtypes of HAE-C1INH exist. Type 1 HAE accounts for 85% of cases and is caused by the inability of the mutated C1 inhibitor protein to be secreted into the blood. Type II HAE accounts for the remaining 15% of cases. The mutant C1 inhibitor protein in type II HAE is secreted but is dysfunctional (i.e. lacks activity). There is usually a family history of angioedema, but some cases are caused by a spontaneous new mutation of the gene at the time of conception.
Swelling can occur in the extremities, abdomen, throat and other organs. Swelling of the airway can be fatal. Abdominal swelling usually involves pain, vomiting and diarrhea. Symptoms usually appear early in life, most often by age 13 and may increase in severity after puberty. Episodes may be spontaneous (that is they occur for no known reason) or triggered by situations such as physical trauma, emotional stress, hormonal factors, infections, or others.
The diagnosis of HAE-C1INH is established by showing low levels of functional C1 inhibitor as well as low levels of C4. In type I HAE, the low antigenic C1 inhibitor levels can substitute for low functional C1 inhibitor levels. In type II HAE antigenic C1 inhibitor levels are normal but functional C1 inhibitor levels are low. Complement levels for C1 and C3 are typically normal.
HAE-nl-C1INH was first described in 2000 and is not yet fully understood. Some patients with HAE-nlC1INH have a mutation in coagulation factor XII, however most patients do not have a known mutation. The C1 inhibitor gene is normal. Like HAE-C1INH, HAE-nl-C1INH runs in families. The age of onset of swelling in HAE-nl-C1INH is typically in the teenage or early adult years. Women are affected more frequently and severely than men. Previously, this was called type III HAE.
Similar to that of HAE-C1INH
The diagnosis of HAE-nl-C1INH is difficult because of the lack of good tests. At the current time, the diagnosis is established by showing the following: normal levels of functional C1 inhibitor as well as normal levels of C4; lack of response to high-dose antihistamines; and either a family history of angioedema or a factor XII mutation.
Acquired C1 inhibitor deficiency occurs in older individuals due to an accelerated destruction of normal C1 inhibitor. Patients develop the acquired deficiency because of an underlying disease state (most commonly a lymphoproliferative disorder), an autoantibody directed against C1 inhibitor, or both. Acquired C1 inhibitor deficiency is not genetic and there is no family history of angioedema.
Similar to that of HAE-C1INH
The diagnosis of acquired C1 inhibitor deficiency is made by the finding of low C1 inhibitor antigen or function with low C4 and generally a low C1 (or C1q) in a patient who presents in middle age or older without a family history of angioedema.
Idiopathic angioedema is the most common type of angioedema and can occur in anyone at any age. Swelling is responsive to antihistamines.
Swelling typically occur in the extremities, face and mouth.
The diagnosis of idiopathic angioedema is made by exclusion of other causes of angioedema
Similar to idiopathic angioedema but not responsive to antihistamines.
Similar to that of idiopathic angioedema, possibly more severe swelling.
Similar to HAE-nlC1INH without a family history or a factor XII mutation.
Angioedema that occurs as part of allergic reaction. Includes anaphylaxis
Swelling of extremities, face, mouth, throat.
The diagnosis of allergic angioedema is made by demonstrating the underlying allergy.
ACE inhibitors are among the most widely prescribed drugs in the world, primarily used for treating hypertension. Angioedema is a side effect of ACE inhibitors, occurring in approximately 1 per thousand patients taking an ACE inhibitor. Certain populations, particularly African-Americans, are at higher risk of suffering from ACE inhibitor-mediated angioedema. The swelling occurs because ACE inhibitor can prolong the half-life of bradykinin in the blood and tissues. It is a class effect seen for all ACE inhibitors and is not an allergic reaction to a specific drug. Patients may be on an ACE inhibitor for years before they suffer their first episode of angioedema. ACE inhibitors are absolutely contraindicated in patients with HAE.
Similar to HAE but with a predilection to involve the face, lips, tongue and oro-pharyngeal-laryngeal areas.
Must be suspected in all patients who experience angioedema while on an ACE inhibitor drug.