A.E.D.A.F. - DISEASE SYNTHESIS

 Definition and Classification

Variant of angioedema, due to a deficiency of the inhibitor of the first component of the Complement System, C1-Inhibitor, which can be caused by a genetic defect (hereditary angioedema) or by excessive consumption (acquired angioedema).

It is estimated that the hereditary form may affect 1 in every 10,000 or 50,000 people. It is transmitted on a dominant autosomal basis (i.e., sons and daughters may inherit it, if their father or mother, or both, have it).

There are few cases of the acquired form, less than 300 in the world.

Disease Symptomatology

Angioedema from C1-inhibitor deficiency may be asymptomatic.

The disorder is usually characterized by swelling lasting from 2 to 5 days, that recurs relatively frequently on a variable basis, and that affects both extremities and internal organs; there is an onset period of progressively increasing intensity of 6 to 24 hours, and it spontaneously subsides or resolves in 12 to 36 hours (without applying treatment). It is not associated with urticaria.

The swelling is white or exhibits a pinkish rash, with compacting of the affected area until it gets very hard and mobility is lost in the area and a period of stability when the skin has a whitish coloring. On occasions it is accompanied by itching or a tingling sensation.

It can affect:

Sweling of the digestive tract causes abdominal pain and vomiting and it can simulate an acute appendicitis.

Sweling of the respiratory tract can cause edema of the glottis with hoarseness and voice loss and in some cases asphyxia.

Precipitating Factors: Traumatisms, Some forms of intense physical exercise (e.g. cycling), Surgical operations, Dental extractions, Fatigue, Insomnia, Stress, Disappointment and distress, Infections, Menstruation, Estrogens (oral contraceptives, hormone replacement therapy), Hypertension drugs of the ECA inhibitor group (IECA).

Diagnosis

Since the disorder may be similar in its presentation to other forms of angioedema caused by allergies or other medical conditions, a correct diagnosis of HAE is very important to avoid potential fatal consequences such as asphyxia or unnecessary abdominal surgery.

As a screening (filtering) technique, levels of C4 are measured, which are lower than normal values both during the crisis period (i.e., swelling) and during periods without symptoms. If these levels low or even normal, the levels of C1-inhibitor and the functional activity of C1-inhibitor must be determined. Low serum levels of C1-inhibitor or of its functional activity confirm the diagnosis.

Treatment

Severe attacks: Intravenous C1-INHIBITOR, from 500 to 1500 units depending on the patient's weight, and if it does not subside shortly depending on the criticality of the affected area, administer another 500 to 1500 units. If this product is NOT available, intravenous transexamic acid may be used although it is much less effective.

Long-term prevention: Attenuated androgens (DANAZOL or STANOZOLOL), or transexamic acid. The dose is personal, indicated by the doctor.

Short-term prevention (surgical operations, dental manipulation, or oropharyngeal procedures): Increase the dose of Danazol/Stanozolol from 6 days before until 3 days after, or administer 500 to 1500 units of intravenous C1-inhibitor, units depending on the patient's weight, 60 minutes before. The choice between attenuated androgens and C1-inhibitor will depend on the severity and localization of the operation. If C1-inhibitor is NOT available, fresh frozen plasma may be administered at least one hour before (preferably 24 hours before) the operation.

Other recommendations:

 

VERY IMPORTANT: antihistamines, corticoids and adrenaline are not effective.