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Angioedema
Angioedema (BE: angiooedema), also known by its eponymQuincke's edema and the older term angioneurotic edema, is the rapid swelling (edema) of the skin, mucosaand submucosal tissues. Apart from the common form, mediated by allergy, it has been reported as a side effect of some medications, specifically ACE inhibitors. Additionally, there is an inherited form, due to deficiency of the blood protein C1-inhibitor. This form is called hereditary angioedema (HAE) or hereditary angio-neurotic edema (HANE), which is due to C1-esterase inhibitor deficiency. Cases where angioedema progresses rapidly should be treated as a medical emergencyas airwayobstruction and suffocationcan occur. Rapid treatment with epinephrine, often with an epi-pen, can be life-saving.
Signs and symptomsThe skin of the face, normally around the mouth, and the mucosa of the mouth and/or throat, as well as the tongue, swell up over the period of minutes to several hours. The swelling can also occur elsewhere, typically in the hands. Sometimes, there has been recent exposure to an allergen(e.g. peanuts), and urticaria(hives) develop simultaneously, but many times the cause is idiopathic(unknown). The swelling can be itchy. There may also be slightly decreased sensation in the affected areas due to compression of the nerves. In severe cases, stridorof the airway occurs, with gasping inspiratory breath sounds and decreasing oxygenlevels. Intubationand rapid treatment with epinephrineand antihistaminesis required in these situations. In hereditary angioedema, there is often no direct identifiable cause, although mild traumaand other stimuli can cause attacks. There is usually no associated itch or urticaria. Patients with this syndrome can also have attacks of recurrent abdominal pain, sometimes leading to an unnecessary laparotomy. There is also an increased incidence of autoimmune disease(e.g. lupus erythematosus, glomerulonephritisand hypothyroidism) due to altered activity of the complement system. DiagnosisThe diagnosis is made on the clinical picture. When the patient has been stabilized, complementlevels, especially C1-inhibitor and depletion of complement factors 2 and 4, may indicate the presence of hereditary angioedema (see below). Additionally, allergy testing should be undertaken to determine if any allergens need to be avoided in the future. If the patient was on ACE inhibitormedication, this has to be discontinued. PathophysiologyThe final common pathway for the development of angioedema seems to be the activation of the bradykininpathway. This peptideis a potent vasodilator, leading to rapid accumulation of fluid in the interstitium. This is most obvious in the face, where the skin has relatively little supporting connective tissue, and edema develops easily. Bradykinin is released by various cell types in response to numerous different stimuli; it is also a painmediator. Various mechanisms that interfere with bradykinin production or degradation can lead to angioedema. ACE inhibitors block the function of kininase II, the enzyme that degrades bradykinin. In hereditary angioedema, bradykinin formation is caused by continuous activation of the complement systemdue to a deficiency in on of its prime inhibitors, C1-esterase inhibitor (C1INH), and continuous production of kallikrein, another process inhibited by C1INH. 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. Additionally, it inhibits various proteins of the coagulationcascade, although effects of its deficiency on the development of hemorrhageand thrombosisappear to be limited. There are three types of hereditary angioedema:
Angioedema can be due to antibodyformation against C1INH; this is an autoimmune disorder. This acquired angioedema is associated with the development of lymphoma. Consumption of foods which are themselves vasodilators such as alcoholor cinnamoncan increase the probability of an angioedema episode in susceptible patients. If the episode occurs at all after the consumption of these foods, its onset may be delayed overnight or by some hours, making the correlation with their consumption somewhat difficult. The use of Ibuprofen may also increase the probability of an episode in some patients. TherapyIn allergic angioedema, avoidance of the allergen and use of antihistamines may prevent future attacks. Cetirizine, marketed as Zyrtec, is a commonly prescribed antihistamine for angioedema. Severe angioedema cases may require desensitization to the putative allergen, as mortality can occur. Chronic cases require steroidtherapy, which generally leads to a good response. In ACE inhibitor use, the medication needs to be discontinued, and all similar drugs need to be avoided. There is a certain degree of controversy whether angiotensin II receptor antagonistsare safe in patients with a previous attack of angioedema. In hereditary angioedema, specific stimuli that have previously luxated attacks may need to be avoided in the future. Severe cases receive replacement therapy with purified vapor-heated C1-esterase inhibitor (as described by Waytes et al 1996), while danazol(an androgen) relieves symptoms somewhat. In the absence of C1inh concentrate, fresh frozen plasmais used. DX-88 is an inhibitor of kallikrein that is due to be marketed as an orphan drugfor hereditary angioedema[1]. HistoryDr Heinrich Quinckefirst described the clinical picture of angioedema in 1882. Sir William Oslerremarked in 1888that some cases may have a hereditary basis; he coined the term hereditary angio-neurotic edema. References
External links
fr:?dème de Quincke
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