Angioedema

Angioedema, also known as angioedema angioneurotic ( after Heinrich Irenaeus Quincke ) and the older term edema, is a rapidly developing in medicine, painless, often itchy swelling ( edema) of the skin, mucous membrane and the adjacent tissue, which on a sudden increase in the permeability of the vessel walls is based. It can last for hours to days. From the urticaria it is distinguished by the participation deeper tissues and the intestinal wall. Almost always there is an allergic reaction or side effect of medications, such as ACE inhibitors. About 6% of diseases are hereditary and based on a lack of the blood protein C1 -esterase inhibitor. This form is called hereditary angioedema (HAE ) or (deprecated) " hereditary angioneurotic edema " ( HANE ) refers. Cases where angioedema progresses rapidly should be treated as a medical emergency, as an obstruction of the respiratory tract and suffocation can occur.

Symptoms and complaints

Within minutes, a swelling arises primarily of eyelids, lips, chin, cheeks, tongue, or genitals. Allergic forms are usually associated with urticaria ( hives) socialized. With participation of the airways, especially the glottis occurs a life-threatening respiratory distress that requires immediate treatment. In hereditary angioedema may also occur with episodes of intestinal edema, which manifests itself in abdominal pain, vomiting and diarrhea.

Diagnosis

The diagnosis is often clinically possible by eye. There often exist typical swelling of the face, mouth and genitals. If necessary, the blood values ​​for C1 inhibitor and a lack of the complement factors 2 and 4 on the existence of an HAE may indicate. Further diagnostics may be similar to those recommended in the case of urticaria measures.

Pathophysiology

The final common pathway for the development of angioedema is probably the activation of Bradykininwegs. This peptide is a potent vasodilator, which leads to a rapid accumulation of fluid in the interstitial space. This is most clearly evident on the face where the skin over relatively little supporting connective tissue features, and edema can easily develop. Bradykinin is released from various cell types in response to a number of different stimuli; it is also a pain mediator. Various mechanisms that influence the formation or degradation of bradykinin disturbing, can lead to angioedema. ACE inhibitors block the function of the kininase II, an enzyme that degrades bradykinin. In hereditary angioedema, the formation of bradykinin on continuous activation of the complement system due to a deficiency of one of its main inhibitors, C1 -esterase inhibitor (C1 - INH), and inhibited by the continuous production of kallikrein, another by C1 -INH process caused. This serine protease inhibitor ( serpin ) normally inhibits the conversion of C1 to C1r and C1s, which - in turn - activate other proteins of the complement system. In addition, it inhibits a variety of proteins of the clotting cascade, although the effects of its deficiency seems to be limited to the development of hemorrhage and thrombosis.

There are three types of hereditary angioedema:

• Type 1 - decreased levels of C1 -INH (85 %);
• Type 2 - normal levels but impaired function of C1 -INH ( 15%);
• Type 3 - no detectable abnormality of C1 -INH, occurs as a dominant inherited disorder, affecting mainly women; they may be aggravated by pregnancy and the use of oral contraceptives ( originally described by Bork et al in 2000, although the exact incidence is uncertain ). Mutations in the F12 gene coding for Hageman factor.

Angioedema may be due to the formation of antibodies against C1 -INH; This is an autoimmune disease. This acquired angioedema is associated with the development of lymphoma.

Therapy

First up is the therapy to avoid the causative agent. For both drugs, foods and physical stimuli come into question. In principle, the angioedema should recede within hours to days completely without residue. Especially in severe cases with involvement of the upper respiratory tract but it is a life-threatening disease that must be treated immediately.

Glucocorticoids and anti- allergens therapy. When infection of the airways glucocorticoids ( cortisone -like substances) and allergy medications administered intravenously or taken in liquid form; in severe cases, an endotracheal intubation is required to ensure the breathability can. In an emergency, also for patients with severe allergic respiratory reactions in the past are adrenaline -filled syringes available, which can be administered intramuscularly even by the person concerned after allergen exposure with incipient symptoms. Otherwise, the treatment is similar to the hives.

Histamine or bradykinin. The therapy is fundamentally different between the histamine-induced urticaria and bradykinin -induced angioedema. While standing for the allergy-related edema antihistamines and cortisone available, these drugs show in the bradykinin -induced angioedema no or only little effect.

Bradykinin. Bradykinin may by genetically related increased bradykinin formation as in hereditary angioedema (HAE ) with C1 esterase inhibitor deficiency and by reducing interference ( eg due to ACE inhibitors ( ACEH ) ) increase.

The C1 -esterase inhibitor inhibits its function, the formation of bradykinin and patients with appropriate C1 -INH deficiency ( type 1, 85%) or dysfunction ( type 2, 15%) suffer throughout their lives recurrent angioedema, which on the skin may occur and the mucous membranes ( head and neck, abdomen) (prevalence 1:10000-1:50000 ). Abdominal angioedema occur, sometimes with nausea and vomiting. Manifestations of upper respiratory tract (tongue, pharynx, larynx) lead to dyspnea, hoarseness, dysphagia up in each individual case by suffocation. BK- induced angioedema typically go hand in hand without itchy urticaria. The therapy is fundamentally different from other edema, which are often histaminergic. The decisive factor is the lack or low efficacy of cortisone or antihistamines. While HAE patients in the acute attack so far i v. C1 INH concentrates were given (human blood plasma product), existed for ACEH induced angioedema far no specific effective pharmacotherapy.

The peptidomimetic icatibant since 2008 is an acute treatment with new therapeutic approach available: works by blocking bradykinin B2 and thus prevents the formation of edema in all types of HAE attacks by blocking the cascade at the beginning.

Therapy C1 -INH deficiency. In C1 -INH deficiency of both glucocorticoids as well as antihistamines are ineffective. Briefly show Epinephrine (adrenaline) by the vasoconstrictive effect decongestant. An effective therapy is only by C1 -INH replacement possible, if not available, fresh frozen plasma ( fresh frozen plasma ) FFP. Further, both anabolic androgens such as danazol and stanozolol used in the long-term therapy. They increase the synthesis of C1 -esterase inhibitor in the liver, but may have significant side effects.

Differential Diagnosis

The usually occurs in early childhood Erythropoietic protoporphyria goes to sun exposure associated with severe swelling. As a frequent misdiagnosis of an allergic reaction with formation of angioedema is created.

History

. Heinrich Quincke first described the clinical picture of angioedema in 1882 Sir William Osler remarked in 1888 that some cases may have a hereditary ( genetic ) basis; he coined the term hereditary angioneurotic edema.