Hereditary angioedema - Symptoms - Treatment

Skin care > Angioedema > Signs and symptoms of hereditary angioedema - Treatment of hereditary angioedema

Hereditary angioedema (HAE) is a rare genetic disorder affecting up to 0.01% of the population with mortality rates estimated at 15–33%.

Hereditary angioedema causes episodic attacks of cutaneous and submucosal swellings affecting the face, extremities, respiratory tract, genitalia, and gastrointestinal tract.

Detecting the early symptoms help in the correct diagnosis, management and treatment of hereditary angioedema. 75% of the clinical HAE symptoms and manifestations are familial inheritance whereas 25% of the symptoms are caused by fresh mutations in the individuals. As the autosomal mutation is a dominant trait, a child has 50 percent chances for inheriting the disorder if one of the parent is affected by angioedema.

Hereditary angioedema types and causative factors

Bradykinin
The primary cause of this hereditary disorder is the increased release of bradykinin, a plasma kinin responsible for raised capillary permeability and leakage, hyperpermeability of small vessels, pain and edema. Low blood plasma levels of functional C1 esterase inhibitor proteins leads to overactivation of the kallikrein-kinin cascade. The overactivated kallikrein-kinin cascade leads to localized release of bradykinin.

Hereditary angioedema - swollen hand

C1-esterase inhibitor (C1-INH)
C1 esterase inhibitor is an important protein regulating the release of bradykinin. Genetic mutations in the C1 inhibitor gene (C1-INH gene or SERPING1 gene), which is mapped to chromosome 11 (11q12-q13.1), can affect or alter the production of normal C1 esterase inhibitor protein.

In type I disorder, gene mutations cause inadequate levels of C1 esterase inhibitor production. 80-85% of hereditary angioedema afflictions come under type I.
In type II disorder, though gene mutations do not lower the production levels of C1 esterase inhibitor protein, the protein produced is ineffective or non-functional in regulating the bradykinin. About 15-20% of of HAE cases come under type II.
In type III disorder, there is no deficiency or inefficiency of C1 esterase inhibitor protein. There is increased levels of kininogenase activity causing increased levels of bradykinin. Increased levels of estrogen hormone can aggravate type III disorder symptoms. Affected Women on oral contraceptives may develop symptoms and have recurrent episodic attacks. They are also susceptible to recurrent episodes during pregnancy. Mutations in F12 gene coding for a serine protease called Factor XII cause type III disorder.

Symptoms of hereditary angioedema

Nonpitting cutaneous swelling is a common symptom affecting the face, hands and legs.
The gastrointestinal afflictions cause edema of the intestinal mucosa leading to symptoms like vomiting, stomach pain and intestinal spasms.
The respiratory tract afflictions can cause blocked airway, suffocation and asphyxiation. Edema of the respiratory tract is a life-threatening emergency requiring treatment at a hospital. Hereditary angioedema patients with the slightest throat or airway swelling symptoms should seek immediate emergency treatment.

Diagnosis of hereditary angioedema

Correct diagnosis of the symptoms of this disorder is vital for proper treatment to avoid potentially fatal consequences. The following symptoms can point to hereditary angioedema.

• Frequent episodic symptoms of angioedema without hives,
• frequent episodes of abdominal pain and vomiting,
• frequent episodes of laryngeal swelling and edema of upper airway and
• familial history of angioedema.

Blood tests taken during the episodes can help in right diagnosis. Quantitative and functional analysis of C1 esterase inhibitor is carried out.
Low C1 esterase inhibitor (C1-INH) level indicate type I.
The diagnosis may be complemented with radiography of the chest and abdomen and ultrasonography and CT scanning.

Hereditary angioedema treatment, management and prophylaxis

Hereditary angioedema does not respond to treatment with antihistamines, corticosteroids, or epinephrine.
Treatment of this hereditary disorder with C1 inhibitor replacement products, plasma kallikrein inhibitor, and bradykinin-receptor antagonist have given significant relief to the patients.

Treatment with plasma derived C1 inhibitor products like C1-INH concentrate replace the deficiency and take over the regulation of the mediating proteins. The nano-filtered C1-INH concentrate, Cinryze, is found to be effective in the treatment of acute episodic attacks.

Treatment with selective bradykinin B2 receptor antagonist, Icatibant, blocks the function of bradykinin.
The kallikrein inhibitor, ecallantide, when used prevents the release of bradykinin.
Attenuated androgens, such as danazol, have been found to reduce the severity as well as frequency of episodes when used on early symptoms. Treatment with these medications induces the body to produce more C1 inhibitor.

Treatment of hypertension with ACE inhibitor (or angiotensin-converting-enzyme inhibitor) drugs is contraindicated in this disorder, as these drugs can cause bradykinin accumulation and trigger the symptoms.
Fresh episodic symptoms may be triggered by dental and surgical procedures, stress, infections and even menstrual cycle. Specific triggers that have previously led to episodes of attacks may need to be avoided to prevent future hereditary angioedema attacks.

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Image source: http://en.wikipedia.org/wiki/File:Swollen_hand_during_a_hereditary_angioedema_attack..jpg
Image author: LucyHAE | License: CC BY-SA 3.0

References:
1.Hemperly, SE; Agarwal, NS; Xu, YY; Zhi, YX; Craig, TJ (July 2013). "Recent Advances in the Management of Hereditary Angioedema". Journal of the American Osteopathic Association 113 (7): 546–555. doi:10.7556/jaoa.2013.006.
2.Zuraw BL, Bernstein JA, Lang DM, et al. A focused parameter update: hereditary angioedema, acquired C1 inhibitor deficiency, and angiotensin-converting enzyme inhibitor-associated angioedema. J Allergy Clin Immunol 2013; 131:1491.

Current topic in the dynamic nature skin care: Hereditary angioedema - types - causes - signs and symptoms - diagnosis - treatment - prevention.