Quincke's edema

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Classification according to ICD-10
T78.3 Angioneurotic edema
- Quincke's edema
ICD-10 online (WHO version 2019)

The angioedema , also known under the older names angioedema (after Heinrich Quincke ) and angioneurotic edema , is a rapidly developing, painless, often itchy swelling ( edema ) of the skin , mucous membrane and the adjacent tissue, the sudden on an increase the permeability of the vessel walls is based. It can last for hours to days. From urticaria , it is distinguished by the participation deeper tissue and the intestinal wall. Almost always it is an allergic reaction or the side effect of medication , such as ACE inhibitors . About 6% of the diseases are hereditary and are based on a deficiency in the blood protein C1 esterase inhibitor . This form is known as hereditary angioedema (HAE) or (outdated) "hereditary angioneurotic edema" (HANE). Spontaneous onset and progression of angioedema are often signs of anaphylaxis , which must be treated immediately as a medical emergency, as respiratory tract obstruction and asphyxiation can occur which, if left untreated, can quickly lead to death.

Characteristic swelling of the face in angioedema

Symptoms and ailments

Within minutes, swelling develops, mainly on the eyelids , lips , chin , cheeks , tongue or genitals . Allergic forms are usually associated with urticaria (hives). If the airways are involved , especially the glottis , life-threatening shortness of breath occurs and requires immediate treatment. When hereditary angioedema can also episodes of intestinal come edema, which is located in abdominal pain manifests, vomiting and diarrhea.

diagnosis

Diagnosis can often be made clinically by visual appearance. There is often typical swelling of the face, mouth and genitals. If necessary, the blood values ​​for C1 inhibitor and a deficiency in the complement factors C2 and C4 can indicate the presence of HAE. Further diagnostics can be similar to the measures recommended in the case of urticaria .

Pathophysiology

The final common pathway to developing angioedema is believed to be through activation of the bradykinin pathway . This peptide is a potent vasodilator that causes fluid to accumulate rapidly in the interstitium. This is most evident in the face, where the skin has relatively little supportive connective tissue and edema can easily develop. Bradykinin is released by different cell types in response to a wide variety of stimuli; it is also a pain mediator . Various mechanisms that interfere with the formation or breakdown of bradykinin can lead to angioedema. ACE inhibitors block the function of kininase II , the enzyme that breaks down bradykinin. In hereditary angioedema , the formation of bradykinin is caused by continuous activation of the complement system due to a lack of one of its main inhibitors, C1-esterase inhibitor (C1-INH), and by the continuous production of kallikrein , another process inhibited by C1-INH , 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. It also inhibits various proteins in the coagulation cascade , although the effects of its deficiency on the development of hemorrhage and thrombosis appear to be limited.

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 dominantly inherited disorder and primarily affects women; it can be made worse by pregnancy and the use of oral contraceptives (originally described by Bork et al in 2000; the exact frequency is uncertain). Is caused by mutations in the F12 - gene , which for the Hageman factor coded.

Angioedema can be due to the formation of antibodies against C1-INH; this is an autoimmune disease . This acquired angioedema is linked to the development of lymphoma .

therapy

The first point of therapy is to avoid the triggering agent. Medicines, foods and physical stimuli can be used for this. In principle, the angioedema should resolve completely without leaving any residue within hours to days. Especially in the case of severe forms with involvement of the upper respiratory tract, it is a life-threatening clinical picture that must be treated immediately.

Glucocorticoids and antiallergenic therapy . If the airways are affected , glucocorticoids ( cortisone- like substances) and antiallergic drugs are administered intravenously or taken in liquid form; in severe cases, endotracheal intubation is required to ensure breathing. For patients with severe allergic reactions of the respiratory tract in the past, adrenaline pre-filled syringes are also available in an emergency , which can be administered intramuscularly by the person concerned after an allergen exposure with the onset of symptoms. Otherwise, the treatment is the same as for hives.

Histamine or bradykinin . Therapy differs fundamentally between histamine-induced urticaria and bradykinin-induced angioedema. While antihistamines and cortisone are available for allergy-related edema, these drugs show little or no effect on bradykinin-induced angioedema.

Bradykinin . Bradykinin can increase due to genetically determined increased bradykinin formation as in hereditary angioedema (HAE) with C1 esterase inhibitor deficiency and due to degradation disorders (e.g. as a result of ACE inhibitors (ACEH)).

The C1 esterase inhibitor inhibits the formation of bradykinin and patients with a corresponding C1-INH deficiency (type 1, 85%) or C1-INH dysfunction (type 2, 15%) suffer from recurrent angioedema for their entire life that can occur on the skin and mucous membranes (head and neck, abdomen) ( prevalence 1: 10000-1: 50000). Abdominal angioedema occurs e.g. Sometimes with nausea and vomiting. Manifestations of the upper respiratory tract (tongue, pharynx, larynx) lead to dyspnoea, hoarseness, difficulty swallowing and, in individual cases, death from suffocation. Bradykinin-induced angioedema is typically associated with no itchy urticaria. The therapy differs fundamentally from other edema, which are often histaminergic. The decisive factor is the lack of or only low effectiveness of cortisone or antihistamines. While HAE patients have so far experienced an acute attack i. v. C1-INH concentrates (human blood plasma product), there has been no specifically effective pharmacotherapy for ACEH-induced angioedema.

With the peptidomimetic Icatibant , an acute therapy with a new therapeutic approach has been available since 2008: The active ingredient blocks the bradykinin receptor B2 and thus prevents the formation of edema in all types of HAE attacks by blocking the cascade right at the beginning.

Therapy of C1-INH deficiency . With C1-INH deficiency, both glucocorticoids and antihistamines are ineffective. For a short time, adrenaline has a decongestant effect due to its vasoconstrictive effect. However, effective therapy is only possible with C1-INH replacement. C1-INH preparations from human plasma (trade names Berinert , Cinryze ) or recombinantly produced as conestat alfa (trade name Ruconest ) are available. If not available, fresh frozen plasma (FFP) can also be used in an emergency. Furthermore, also anabolic acting androgens such as danazol and stanozolol used in long-term therapy. They increase the synthesis of C1 esterase inhibitor in the liver, but can have significant side effects.

Differential diagnosis

The erythropoietic protoporphyria , which usually occurs in early childhood, is associated with severe swellings after exposure to the sun. Frequently the misdiagnosis of an allergic reaction with the development of angioedema is made.

history

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

literature

Guidelines

Others

Individual evidence

  1. ↑ Angioedema, hereditary, type III.  In: Online Mendelian Inheritance in Man . (English)

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