Introduction:
Angioneurotic oedema is associated with rapid swelling of dermis, subcutaneous tissue, mucosa and submucosal tissues. It should be differentiated from urticaria where oedema occurs in the upper dermis. The term angioneurotic oedema is a misnomer which was used with the belief that nervous system was involved in some way as a causative factor. It was first introduced by Quinke in 1882. It was in 1888 Osler came out with a complete description of hereditary angioneurotic oedema.
The progression of angioneurotic edema could be very rapid and could even be life threatening. Major danger is airway compromise.
Classification:
Angioneurotic oedema can be classified into
Hereditary
Acquired.
Acquired angioneurotic oedema:
This is commonly caused by allergy and is usually associated with allergic symptoms like urticaria. It can also occur as a side effect to certain drugs (ACE inhibitors).
Hereditary angioneurotic oedema:
As the name suggests it is hereditary and is inherited as autosomal dominant form. This type is known to exist in three forms distinguished according to the underlying gene involvement. The first and the second forms as caused by abnormalities / mutations of SERPING1 gene. These mutations can cause decrease in the circulating levels of C1-inhibitor protein (type I hereditary anginoneurotic oedema) or dysfunctional forms of the same protein (this is type II hereditary angioneurotic oedema). Type III hereditary angioneurotic oedema is associated with mutations of F12 gene. This gene is supposed to encode the coagulation factor 12. Almost all these forms of hereditary angioneurotic odema cause abnormal activation of complement system and cause swelling / oedema in other regions of the body like digestive tract. If this swelling involves larynx it can compromise the airway.
Signs / symptoms:
The following areas may become swollen within minutes to hours:
Skin of the face and around the mouth
Mucosa of mouth and throat
Tongue
Hands
Decreased sensation due to compression of nerves
Airway compromise / stridor
In acquired angioneurotic oedema exposure history of allergen can be elicited
In hereditary angioneurotic oedema there is not obvious cause. It could be as trivial as mild trauma / dental scaling etc. These patients do not exhibit urticaria / allergic rashes as it is not an allergic response. These patients may manifest with acute abdominal pain and watery diarrhoea. Acute abdominal pain is also associated with lymphocytosis. Swelling may also occur in the extremities.
Investigations:
Complete blood count
Renal function tests
Serum electrolyte estimation ( in cases of diarrhoea)
Mast cell tryptase levels may be raised in acquired angioneurotic oedema
Deficiency of C1 inhibitor
Depletion of complement factors 2 and 4 indicate deficiency of C1 inhibitor
Hereditary angioneurotic oedema can be identified when the patient fails to respond to antihistamines and steroids.
Pathophysiology:
Bradykinin plays a vital role in the pathogenesis of all forms of angioneurotic oedema. This peptide is a potent vasodilator which increases vascular permeability causing rapid accumuation of fluid in the interstitium. Reducing / blocking this peptide plays a vital role in alleviating the symptoms.
ACE inhibitors block ACE the enzyme that is responsible for deactivation of bradykinin. It should be borne in mind that bradykinin is produced by continuous activation of complement system. Complement system is continuosly activated by deficiency of C1 esterase which is a potent inhibitor of complement system. This is made possible due to continuous production of Kallikrein.
Differences between the three types of hereditary angioneurotic odemea:
Type I : Decreased levels of C1 inhibitor
Type II : Normal levels of C1 inhibitor but decreased function
Type III : There is no abnormality involving C1 inhibitor, and is an X linked dominant disorder mainly affecting females. This condition can be exacerbated by pregnancy / contraceptive pills and other hormone therapy.
Aggravating factors:
Consumption of food that causes vasodilatation (alcohol / cinnamon)
Use of Ibuprofen / aspirin may increase the probablity in some patients
Use of Bromelain in combination with turmeric has been proved to be beneficial in certain cases.
Management:
Allergic – In allergy induced angioneurotic oedema avoidance of allergen and use of antihistamines may prevent future attacks. Cetrizine is the commonly prescribed antihistamine in the management of allergic angioneurotic oedema. Severe allergic angioneurotic oedema may require desensitization if the putative allergen could be identified. Use of steroids have also found to be beneficial in these patients.
Drug induced angioneurotic oedema: Common drugs involved include ACE inhibitor. Avoidance of these drugs will help.
Hereditary angioneurotic oedema : Since C1 Inhibitor is deficient in these patients C1 inhibitor concentrates can be administered. In acute cases frozen plasma may be beneficial as it contains adequate amounts of C1 inhibitor.
