Edema of Quincke

The angio-edema , known also by its éponyme edema of Quincke and the old term edema angioneurotic , is the swelling (edema) fast of the Peau, the Muqueuses and under-mucous fabrics. Apart from the current form, due to a Allergy, it was observed among the undesirable effects of some Médicament S, and in particular the inhibiting of the ECA.

In addition, there exists a hereditary form, due to the deficit in C1-Inhibiter of blood protein. This form is called “hereditary angio-edema” (“AOH”), which is due to the deficit in inhibiter of C1-estérase. It is sometimes called by the obsolete term “hereditary edema angioneurotic” (OANH), because one supposed that it was purely related to the stress caused by an emotional traumatism and/or neuroses. This vague image of the AOH led many patients to be qualified wrongly the unstable mental ones; one often refused to treat their symptoms which were atrociously painful, in particular in the event of swelling inside the gastro-intestinal apparatus, of the bladder and the reproductive bodies. Modern medicine since then discredited this theory, thus withdrawing the term “neurotic” of its name.

The cases where the angio-edema progresses quickly must be treated like Medical emergency since an obstruction of the air Routes and a Suffocation can occur. A fast treatment by the Adrenalin, often with a Ear-PEN, can save the life.

Signs and symptoms

Skin of the face, normally around the mouth and the oral mucous membrane and/or the throat, as well as the Langue swell during a few minutes or several hours. Swelling can also occur elsewhere, generally on the hands. Sometimes, the patient was recently exposed with a Allergène (e.g. Cacahuète S), and a Urticaire develops simultaneously; but very often, the origin is Idiopathique (unknown). Swelling can cause a itching. There can also be a light reduction in the feelings in the affected areas, because of the compression of the nerves.

In the serious cases, a Stridor of the air routes occurs, with halètements with the inspiration and a fall of the rates of Oxygène. A Intubation trachéale and a fast treatment by Adrenalin and Antihistaminique S are necessary in these cases.

In the hereditary angio-edema, there does not exist often any identifiable direct cause, although light traumatisms and other stimuli can be at the origin of the crises. Generally, no itching nor urticaria is associated with the crises, since it is not a question of an allergic reaction. The patients with AOH can have recurring episodes (often called “crises”) of internal swelling, causing serious abdominal pains, usually accompanied by intense vomiting, weaknesses, and in certain cases of aqueous diarrhea, and of a cutaneous rash, nonpruriginous, in the shape of spot/swirl. The gastric crises can last from 1 to 5 days on average, and can require a hospitalization for an effective assumption of responsibility of the pain and hydration. The abdominal crises are known to cause a significant growth of the leucocytic numeration of the patients, usually about 13-30,000. As the symptoms start to regress, numeration also starts it to decrease slowly, being standardized since the crisis yields.

The AOH causes also a swelling at various other places, most of the time, on the level of the members, genitals, neck, throat and face. The pain associated with these swellings varies the unpleasant one to atrocious, according to the localization and of severity.

Diagnosis

The diagnosis is established on the basis of clinical picture. When the patient was stabilized, the rates of the complement, and in particular C1-Inhibiter and déplétion of the factors of complement 2 and 4, can indicate the presence of a hereditary angio-edema (see below).

As several years can be passed without the AOH not being diagnosed at the majority of the people who suffer from it, and with many erroneous diagnoses, the useless abdominal surgery is current. The perplexed doctors often carry out an exploratory laparascopy and in rare cases, the ablation of a section of the intestine.

Pathophysiology

The final current way for the development of the angio-edema seems to be the activation of the way of the Bradykinine. This Peptide is powerful a Vasodilatateur, involving a fast accumulation of fluid in interstitium. This is most obvious on the face, where the skin has relatively few conjunctive Tissu of support and the edema develops easily. The bradykinine is released by various types of cells, in answer to many different stimuli; it is also a mediator of the Douleur.

Various mechanisms interfering with the production or the degradation of the bradykinine can induce an angio-edema. The inhibiters of the ECA block the function of the Kininase II, the enzyme which degrades the bradykinine. In the hereditary angio-edema, the formation of bradykinine is caused by activation continues Système of the complement due to a deficit in one of its principal inhibiters, the inhibiter of C1 estérase (C1INH), and the production continues Kallikréine, another process inhibited by C1INH. This Inhibiteur of proteases with serine (serpin) normally inhibits the conversion of C1 with C 1r and C1s, which - in its turn - active of other proteins of the system of the complement. Moreover, it inhibits various proteins of the cascade of Coagulation, although the effects of its deficit on the development of the Hémorragie and the Thrombose seem to be limited.

There exist three types of hereditary angio-edema:

Standard 1 - reduced taxes of C1INH (85%);
Standard 2 - normal levels of C1INH but reduced function (15%);
Standard 3 - nondetectable anomaly of C1INH, occurs in a mode dominating Lié on X, consequently assigning primarily the women; it can be exacerbated by the Grossesse and the use of Contraceptifs oral examinations (initially described by Bork et al. in 2000, dubious exact frequency);

The angio-edema can be due to the formation of Anticorps against C1INH; it is what one calls a auto-immune Affection. This “acquired angio-edema” is associated with the development of a Lymphome.

The food consumption which is themselves of the vasodilators such as the alcoholic drinks or the grooves can increase the probability of an episode of angio-edema among predisposed patients. If the crisis occurs after the consumption of this food, its appearance can be delayed day at the following day or of a few hours, returning the correlation with their more difficult consumption.

The use of Ibuprofène or Aspirine can increase the probability of crisis among certain patients. The use of Acétaminophène involves an increase certainly more reduced but real in the probability of crisis.

Treatment

In the case of the allergic angio-edema, the absence of exposure to the allergen and the use of antihistamines are likely to prevent the future crises. The Cétirizine, marketed under the name of Zyrtec, is an antihistamine usually prescribed in the event of angio-edema. The severe cases of angio-edema can require a desensitizing with the putative allergen, taking into account the risk of mortality. The chronic cases require a therapy by steroids, generally involving an good answer.

In the event of use of an inhibiter of the ECA, the drug must be stopped and all the similar drugs must be avoided. A discussed debate treats because of knowing if the Antagonistes of the receiver of angiotensin II can be used in full safety among patients having had former crises of angio-edema.

In the case of the hereditary angio-edema, it is advisable possibly in the future to avoid the specific stimuli which started the crises beforehand. The serious cases receive a substitution therapy by the inhibiter of C1-estérase (as described by Waytes et al. 1996) which is approved in certain countries, such as Berinert P, while the Danazol (a Androgène) relieves the symptoms somewhat. The concentrate of C1inh is not available to the United States, therefore one uses sometimes fresh Plasma frozen. The concentrate of C1inh is currently in last phase of development, for the use in the event of acute crisis and in prevention and at the time of an acute study. DX-88 is an inhibiter of the kallikréine under development like orphan Médicament for the hereditary angio-edema. The Icatibant is a selective antagonist of the receiver of the bradikinine, which must be marketed as orphan drug for the hereditary angio-edema by Jerini AG, a German pharmaceutical company. Pharming, a Dutch company of biotechnology develops a C1 inhibiter recombining for the acute crises of hereditary angio-edema. The product rhC1INH of Pharming and icatibant it of Jerini are currently at the stage III of the development and profit from the statute of orphan Médicament in the United States and in Europe.

In types I and II of acquired angio-edema, and angio-edema nonhistaminergic, the antifibrinolytiques ones such as the tranexamic Acid or the ε-aminocaproïque acid can be effective.

History

Dr. Heinrich Quincke described for the first time the clinical picture of the angio-edema in 1882. Sir William Osler noticed in 1888 that certain cases could have a hereditary base; he thus invented the term “edema angio-neurotic hereditary”.

References

Bork K, Barnstedt SE, Koch P, Traupe H. Hereditary angioedema with normal C1-inhibiter activity in women. Lancet 2000;356: 213-7. PMID 10963200.
Osler W. Hereditary angio-neurotic edema. Am J Med Sci 1888; 95: 362-67.
Quincke H. Concerning the acute localized edema off the skin. Monatsh Prakt Derm 1882;1: 129-131.
Waytes AT, Rosen FS, Frank Misters Treatment off hereditary angioedema with has vapor-heated C1 inhibiter concentrate. NR Engl J Med 1996; 334: 1630-4. PMID 8628358.

See too

Urticaria
edema of the pharynx
cutaneous Allergy
List of the principal allergens

External bonds

(C1INH)
(standard hereditary angio-edema 1/2)
(standard 3)
Emedicine article on the angio-edema
US Hereditary Angioedema Association

Category: Auto-immune disease Category: Dermatology

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