( '''Quincke's edema''' and the older term '''angioneurotic edema''', is the rapid swelling (
Edema ) of the
Skin ,
Mucosa and submucosal tissues. Apart from the common form, mediated by
Allergy , it has been reported as a side effect of some
Medication s, specifically
ACE Inhibitor s. 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 Emergency as
Airway obstruction and
Suffocation can occur. Rapid treatment with
Epinephrine , often with an
Epi-pen , can be life-saving.
The 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.
Peanut s), and
Urticaria (hives) develop simultaneously, but many times the cause is
Idiopathic (unknown). The swelling can be
Itch y. There may also be slightly decreased sensation in the affected areas due to compression of the nerves.
In severe cases,
Stridor of the airway occurs, with gasping inspiratory breath sounds and decreasing
Oxygen levels.
Intubation and rapid treatment with
Epinephrine and
Antihistamine s is required in these situations.
In hereditary angioedema, there is often no direct identifiable cause, although mild
Trauma and 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 ,
Glomerulonephritis and
Hypothyroidism ) due to altered activity of the
Complement System .
The diagnosis is made on the clinical picture. When the patient has been stabilized,
Complement levels, 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 Inhibitor medication, this has to be discontinued.
The final common pathway for the development of angioedema seems to be the activation of the
Bradykinin pathway. This
Peptide is 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
Pain mediator.
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 System due 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
Coagulation cascade, although 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 C1INH (85%);
- Type 2 - normal levels but decreased function of C1INH (15%);
- Type 3 - no detectable abnormality in C1INH, occurs in an X-linked dominant fashion and therefore mainly affects women; it can be exacerbated by Pregnancy and use of Oral Contraceptive s (originally described by Bork ''et al'' in 2000, exact frequency uncertain);
Angioedema can be due to
Antibody formation 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
Alcohol or
Cinnamon can 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 or
Aspirin may increase the probability of an episode in some patients. The use of
Acetaminophen typically has a smaller, but still present, increase in the probability of an episode.
In 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
Steroid therapy, 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 Antagonist s are 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 Plasma is used. DX-88 is an inhibitor of kallikrein that is due to be marketed as an
Orphan Drug for hereditary angioedema
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Dr
Heinrich Quincke first described the clinical picture of angioedema in
1882 . Sir
William Osler remarked in
1888 that some cases may have a hereditary basis; he coined the term ''hereditary angio-neurotic edema''.
- Bork K, Barnstedt SE, Koch P, Traupe H. ''Hereditary angioedema with normal C1-inhibitor activity in women.'' Lancet 2000;356:213-7. PMID 10963200.
- Osler W. ''Hereditary angio-neurotic oedema.'' Am J Med Sci 1888;95:362-67.
- Quincke H. ''Concerning the acute localized oedema of the skin.'' Monatsh Prakt Derm 1882;1:129-131.
- Waytes AT, Rosen FS, Frank MM. ''Treatment of hereditary angioedema with a vapor-heated C1 inhibitor concentrate.'' N Engl J Med 1996;334:1630-4. PMID 8628358.
