血管性水肿

症状

The skin of the face, normally around the mouth, and the mucosa of the mouth and/or throat, as well as the tongue, swell over the period of minutes to hours. The swelling can also occur elsewhere, typically in the hands.  The swelling can be itchy or painful.  There may also be slightly decreased sensation in the affected areas due to compression of the nerves. Urticaria (hives) may develop simultaneously.
In severe cases, stridor of the airway occurs, with gasping or wheezy inspiratory breath sounds and decreasing oxygen levels. Tracheal intubation is required in these situations to prevent respiratory arrest and risk of death.
Sometimes, the cause is recent exposure to an allergen (e.g. peanuts), but more often it is either idiopathic (unknown) or only weakly correlated to allergen exposure.
In hereditary angioedema, often no direct cause is identifiable, although mild trauma, including dental work and other stimuli, can cause attacks. There is usually no associated itch or urticaria, as it is not an allergic response.  Patients with HAE can also have recurrent episodes (often called "attacks") of abdominal pain, usually accompanied by intense vomiting, weakness, and in some cases, watery diarrhea, and an unraised, nonitchy splotchy/swirly rash.  These stomach attacks can last one to five days on average, and can require hospitalization for aggressive pain management and hydration. Abdominal attacks have also been known to cause a significant increase in the patient's white blood cell count, usually in the vicinity of 13,000 to 30,000.  As the symptoms begin to diminish, the white count slowly begins to decrease, returning to normal when the attack subsides. As the symptoms and diagnostic tests are almost indistinguishable from an acute abdomen (e.g. perforated appendicitis) it is possible for undiagnosed HAE patients to undergo laparotomy (operations on the abdomen) or laparoscopy (keyhole surgery) that turns out to have been unnecessary.
HAE may also cause swelling in a variety of other locations, most commonly the limbs, genitals, neck, throat and face. The pain associated with these swellings varies from mildly uncomfortable to agonizing pain, depending on its location and severity. Predicting where and when the next episode of edema will occur is impossible. Most patients have an average of one episode per month, but there are also patients who have weekly episodes or only one or two episodes per year. The triggers can vary and include infections, minor injuries, mechanical irritation, operations or stress. In most cases, edema develops over a period of 12–36 hours and then subsides within 2–5 days.

诊断

The diagnosis is made on the clinical picture. Routine blood tests (complete blood count, electrolytes, renal function, liver enzymes) are typically performed. Mast cell tryptase levels may be elevated if the attack was due to an acute allergic (anaphylactic) reaction. When the patient has been stabilized, particular investigations may clarify the exact cause; complement levels, especially depletion of complement factors 2 and 4, may indicate deficiency of C1-inhibitor. HAE type III is a diagnosis of exclusion consisting of observed angioedema along with normal C1 levels and function.
The hereditary form (HAE) often goes undetected for a long time, as its symptoms resemble those of more common disorders, such as allergy or intestinal colic. An important clue is the failure of hereditary angioedema to respond to antihistamines or steroids, a characteristic that distinguishes it from allergic reactions. It is particularly difficult to diagnose HAE in patients whose episodes are confined to the gastrointestinal tract. Besides a family history of the disease, only a laboratory analysis can provide final confirmation. In this analysis, it is usually a reduced complement factor C4, rather than the C1-INH deficiency itself, that is detected. The former is used during the reaction cascade in the complement system of immune defense, which is permanently overactive due to the lack of regulation by C1-INH.
Angioedema is classified as either hereditary or acquired.

获得性血管性水肿

Acquired angioedema (AAE) can be immunologic, nonimmunologic, or idiopathic. It is usually caused by allergy and occurs together with other allergic symptoms and urticaria. It can also occur as a side effect to certain medications, particularly ACE inhibitors. It is characterized by repetitive episodes of swelling, frequently of the face, lips, tongue, limbs, and genitals. Edema of the gastrointestinal mucosa typically leads to severe abdominal pain; in the upper respiratory tract, it can be life-threatening.

遗传型血管性水肿

Hereditary angioedema (HAE) exists in three forms, all of which are caused by a genetic mutation inherited in an autosomal dominant form. They are distinguished by the underlying genetic abnormality. Types I and II are caused by mutations in the SERPING1 gene, which result in either diminished levels of the C1-inhibitor protein (type I HAE) or dysfunctional forms of the same protein (type II HAE). Type III HAE has been linked with mutations in the F12 gene, which encodes the coagulation protein factor XII. All forms of HAE lead to abnormal activation of the complement system, and all forms can cause swelling elsewhere in the body, such as the digestive tract. If HAE involves the larynx, it can cause life-threatening asphyxiation. The pathogenesis of this disorder is suspected to be related to unopposed activation of the contact pathway by the initial generation of kallikrein and/or clotting factor XII by damaged endothelial cells. The end product of this cascade, bradykinin, is produced in large amounts and is believed to be the predominant mediator leading to increased vascular permeability and vasodilation that induces typical angioedema "attacks".

过敏

In allergic angioedema, avoidance of the allergen and use of antihistamines may prevent future attacks. Cetirizine is a commonly prescribed antihistamine for angioedema.  Some patients have reported success with the combination of a nightly low dose of cetirizine to moderate the frequency and severity of attacks, followed by a much higher dose when an attack does appear.  Severe angioedema cases may require desensitization to the putative allergen, as mortality can occur. Chronic cases require steroid therapy, which generally leads to a good response. In cases where allergic attack is progressing towards airway obstruction, epinephrine may be life-saving.

药物导致

ACE inhibitors can induce angioedema. ACE inhibitors block the enzyme ACE so it can no longer degrade bradykinin; thus, bradykinin accumulates and causes angioedema. This complication appears more common in African-Americans. In people with ACE inhibitor angioedema, the drug needs to be discontinued and an alternative treatment needs to be found, such as an angiotensin II receptor blocker (ARB) which has a similar mechanism but does not affect bradykinin. However, this is controversial, as small studies have shown some patients with ACE inhibitor angioedema can develop it with ARBs, as well.

遗传性

In hereditary angioedema, specific stimuli that have previously led to attacks may need to be avoided in the future. It does not respond to antihistamines, corticosteroids, or epinephrine. Acute treatment consists of C1-INH (C1-esterase inhibitor) concentrate from donor blood, which must be administered intravenously. In an emergency, fresh frozen blood plasma, which also contains C1-INH, can also be used. However, in most European countries, C1-INH concentrate is only available to patients who are participating in special programmes. The medications ecallantide and icatibant may be used to treat attacks. In 2017 these medications cost between 5,700 and 14,000 美元 per dose in the United States, prices that tripled in two years.
Future attacks of hereditary angioedema can be prevented by the use of androgens such as danazol, oxandrolone or methyltestosterone. These agents increase the level of aminopeptidase P, an enzyme that inactivates kinins; kinins (especially bradykinin) are responsible for the manifestations of angioedema.
活性减弱的雄性激素如达那唑、司坦唑（康力龙）、羟甲烯龙（康复龙）等治疗先天性C1INH缺陷，可纠正其生化缺损并有预防发作的效用，但不能用于小儿和孕妇。

获得性

获得性血管神经性水肿、HAE的I型与II型、以及非组胺血管神经性水肿性，抗纤维蛋白溶酶药物如氨甲环酸或ε-氨基己酸有时可控制自然发作，也适用于小儿和孕妇。桂利嗪可用于抗C4活化，适用于有肝病不能使用雄性激素的患者。

历史

1882年，Heinrich Quincke首次临床报告此病。 虽然有些更早的临床描述。
1888年，William Osler认为某些是由于遗传导致的，称“遗传性血管神经性水肿”。
1963年证实了C1酯酶抑制剂匮乏是病因。

流行病学

在美国，急诊室年度就诊患者中有80,000至112,000是血管神经性水肿，是过敏导致就医中的首位。